Atlas of Genetics and Cytogenetics in Oncology and Haematology


Home   Genes    Leukemias    Solid Tumours    Cancer-Prone    Deep Insight    Case Reports    Journals   Portal    Teaching   

X Y 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 NA
    

Visualize Dynamic Chromosome

 

Eisuke Gotoh1*,2

1 Division of Genetic Resources, National Institute of Infectious Diseases Japan, 1-23-1, Toyama, Shin-juku-ku, Tokyo, 162-8640, Japan
2 Department of Radiology, Jikei University of School of Medicine, 3-25-8, Nishi-Simbashi, Minato-ku, Tokyo, 116, Japan
* Corresponding Address: Division of Genetic Resources, National Institute of Infectious Diseases Japan, 1-23-1, Toyama, Shin-juku-ku, Tokyo, 162-8640, Japan
e-mail: egotoh@nih.go.jp

 

January 2011

 

 

 

Key words: chromosome condensation/compaction, chromosome structure, DNA replication, cell cycle, mitosis, S-phase, premature chromosome condensation (PCC), prematurely condensed chromosomes (PCCs), calyculin A, beads loading method

A most miracle mysterious and profound event in eukaryote cell is how DNA folds to chromosomes. In human diploid cell (2n), for example, the total DNA (~6x109 nucleotide base pairs, a meter of length when fully relaxed) is packed to 46 chromosomes (22 pairs of autosomes and 1 pair of sex chromosomes) and contained in nuclei size of ~5 μm in diameter (Alberts et al., 1989). It is quite difficult to imagine how such long length thin fibrous linear molecule is folded in small sized chromosomes without entangling in a narrow nucleus space. Very earlier, the concept about the chromosome architecture formation during cell cycling was conceived as follows: (1) chromosomes are diffused over nucleus as decondensed form in G1-phase (Gap 1 phase), (2) DNA synthesis starts and chromosome replicates in S-phase (Synthesis of DNA phase), (3) DNA synthesis finished, the resulted chromosomes are duplicated and ready for cell division in G2-phase (Gap 2 phase) and then (4) chromosomes condense: separation/segregation and cell division occurs in M-phase (Mitotic phase). This traditional concept seems to tell that DNA replication and chromosome condensation are independent events that proceed in S- and M- cell cycle stage, respectively.
Recently, number of accumulated evidences suggests a close relationship between DNA replication and chromosome condensation. Premature chromosome condensation (PCC) technique was introduced in the 1970's as a useful technique that allows the interphase nuclei to be visualized as condensed mitotic chromosome (Johnson and Rao, 1970; Johnson et al., 1970; Sperling and Rao, 1974). Since then, a lot of studies including DNA replication and chromosome packaging have been archived using the PCC method (Hittelman and Rao, 1976; Rao et al., 1977; Hanks and Rao, 1980; Mullinger and Johnson, 1980; Lau and Arrighi, 1981; Mullinger and Johnson, 1983). These studies seem to teach that the different DNA packaging appearance in different sub-phase of S-phase suggest that the degree of chromosome condensation might be tightly coupled with the progressing of DNA replication. However, the limited available methodologies at that time did not allow the precise mechanism to be cleared.
More recently, accumulated evidences have further concrete that eukaryote DNA replication/transcription is involved in compaction of chromosomes (Zink et al., 1998; Manders et al., 1999; Samaniego et al., 2002, Pflumm, 2002). Molecular genetic studies have also provided supporting evidence for the idea that mutation (in genes as HIRA/Tuple1, XCDT1, cdt1, Orc2, Orc3, Orc5, MCM2, MCM4, MCM10, RECQL4, required for DNA replication) showed abnormal phenotype in chromosome condensation (Loupart et al., 2000; Maiorano et al., 2000; Nishitani et al., 2000; Pflumm and Botchan, 2001; Christensen and Tye, 2003; McHugh and Heck, 2003; Prasanth et al., 2004), inherited diseases (D'Antoni et al., 2004; Sangrithi et al., 2005), genomic instability or prone to cancer (Tatsumi et al., 2006; Pruitt et al., 2007; Shima et al., 2007), or aberrant replication timing causes abnormal chromosome condensation (Loupart et al., 2000; Marheineke and Hyrien, 2001; Pliss et al., 2009). For more detailed knowledge about the DNA replication, see also the following excellent reviews; Bell and Dutta, 2002 and Masai et al., 2010.
In the present article, using drug-induced PCC technique and direct Cy3-dUTP fluorescent replicating DNA by beads loading method, we demonstrate the dynamics of chromosome structure, formation and transition during the S-phase progression in which tight-coupled relation between DNA replication and chromosome condensation /compaction. Possible hypothetical chromosome condensation/compaction model involving the role of DNA replication will be suggested.

Chromosome dynamics: DNA replication, condensation, decondensation, cohesion, separation, segregation, cytokinesis etc.

Under a quite stringent and higher ordered mechanism, chromosomes condense during mitosis within a very short lapse of time in the mitotic phase. Mitotic phase is further divided into several subphases (preprophase, prophase, prometaphase, metaphase, anaphase and telophase), followed by cytokinesis. In the course of Mitotic phase, number of sequential drastic conformational transactions are proceeded as following: (1) chromatins condense to well-defined visible chromosomes under the microscope (2) mitotic spindle assemble begin, nuclear envelope breakdown into membrane vesicles, centriole and mitotic spindle formation followed by spindle attaches to chromosome centromeres (3) kinetocore microtubules align the chromosomes at metaphase plate (4) chromosome separation segregates to spindle poles (5) separated daughter chromatids reach the poles followed by the nuclear envelope re-forms (6) formation of contractile ring and cleavage furrows which constrict the cell center, cytokinesis, cell dividing into two daughter cells, chromosome decondensation in divided cells and finally re-entering the cells in the G1 phase (Alberts et al., 1989). The detailed of the whole mechanism is still almost unclear. However, number of molecules which involved in the mitotic events have been identified such as SMC proteins, including condensin (chromosome condensation), cohesion (chromosome cohesion of replicated chromosomes) (Swedlow and Hirano, 2003), NuMA protein for spindle pole formation (Chang et al., 2009; Haren et al., 2009; Silk et al., 2009; Torres et al., 2010), nuclear lamins (Moir et al., 2000), aurora kinases in centromere function (Tanno et al., 2006; Meyer et al., 2010; Tanno et al., 2010), shugoshin and protein protein phosphatase 2A in chromosome cohesion (Kitajima et al., 2006; Tanno et al., 2010), cdk1 in chromosome condensation, chromosome bi-orientation (Tsukahara et al., 2010), cyclin B, cdc2, cdc25 in chromosome condensation (Masui, 1974; Draetta and Beach, 1988; Dunphy et al., 1988; Kumagai and Dunphy, 1992), Polo and Rho in cytokinesis (Burkard et al., 2009; Wolfe et al., 2009; Li et al., 2010) and many other proteins. Chromosome dynamic consists of such number of various elements. Regarding these dynamics, numerous visualizing studies reported or in progression are achieved through the mitosis events, relatively easy to observe under microscope. However, visualizing approaches in chromosome dynamics, coupled with DNA replication, is still limited. This restraint is due to difficulties as to observe the chromosomes in the S-phase: chromosomes are usually invisible at this stage, since they are decondensed. In the present review, we simply focus on visualizing the chromosome dynamics coupled with DNA replication during the S-phase progression and we show how replicating DNA is folded into higher order chromosomes.

Tools to visualize the dynamic chromosomes

  • Drug-induced premature chromosome condensation (PCC) method

    Cytogenetic analysis studies are usually performed on chromosomes. As condensed in mitosis, chromosomes are usually visible, but as they decondensed in the interphase, they are invisible (Manders et al., 1996; Gotoh and Durante, 2006). Therefore, it is practically difficult or even impossible to analyze the dynamics of chromosome condensation during the interphase by conventional chromosome methods such as colcemid block. Premature chromosome condensation (PCC) is a useful and a unique technique that allows the interphase nuclei to be visualized as a condensed form of mitotic chromosome (Johnson and Rao, 1970; Rao and Johnson, 1970). Conventional PCC has been carried out by cell fusion using either fusogenic viruses (i.e. Sendai virus) (Johnson and Rao, 1970) or polyethylene glycol (PEG) (Pantelias and Maillie, 1983) (cell fusion-mediated PCC). But these protocols are usually technically demanding and keenly depend on the activity of the virus or PEG. Virus-mediated PCC might be also problematic because of infectious viruses use. Moreover, resulting chromosomes are mixture of those inducer and recipient cells (Gotoh and Durante, 2006). Due to these restrictions, conventional PCC has been used in limited institutions. These drawbacks of the conventional PCC technique have been recently overcome with a much easier and more rapid technique using calyculin A or okadaic acid, specific inhibitors of protein phosphatases (drug-induced PCC technique) (Gotoh et al., 1995; Gotoh and Asakawa, 1996; Asakawa and Gotoh, 1997; Durante et al., 1998; Gotoh and Durante, 2006). Drug-induced PCC is becoming now 'popular' and has been used in a wide range of cytogenetic applications (Gotoh and Asakawa, 1996; Asakawa and Gotoh, 1997; Gotoh et al., 1999; Ito et al., 2002; Terzoudi et al., 2003; El Achkar et al., 2005; Gotoh and Tanno, 2005; Gotoh et al., 2005; Srebniak et al., 2005; Terzoudi et al., 2005; Deckbar et al., 2007; Gotoh, 2007; Beucher et al., 2009; van Harn et al., 2010). Thus, drug-induced PCC technique is suitable to visualize dynamic chromosomes particularly in interphase nuclei. This technique will be also useful and applicable in many fields of cytogenetic approaches including traditional chromosome analysis study, because the technique is very simple and much easier even than the conventional colcemid blocking method (Gotoh, 2009).

  • Beads loading method

    Cytogenetically visualization of the replicating DNA is certainly a most direct approach to identify the DNA replication dynamics. In the very earlier studies, the fibre autoradiography of DNA had been labeled with 3H-thymidine (Fakan and Hancock, 1974; Edenberg and Huberman, 1975; Hand, 1978). The spatial resolution of fibre autoradiography is, however, limited because the location of the silver grains, developed in photosensitive emulsion layer and covered the specimens, do not correctly reflect the actual regions of the foci incorporating the 3H-thymidine and the size of grains are not enough tiny to determine the precise location of replicating regions. More precise localization and measure the replication foci were then done using thymidine analog BrdU (Bromodeoxy Uridine) labeling and its antibodies (Nakamura et al., 1986; Mills et al., 1989; Nakayasu and Berezney, 1989). However, the resolution is still limited presumably because it is based on accessibility problems or size of immunocomplex (antigen/antibodies). Recently, the replication regions and chromosome formation in living cells were visualized using Cy5-dUTP directly labeled fluorescent DNA (Manders et al., 1999) by beads loading methods (McNeil and Warder, 1987). The procedure facilitate the analogues (Cy3-dUTP or Cy5-dUTP) to be incorporated in the cell nucleus in a very short time whereby transiently permeabilizes the cell membranes. This method allows the replicating DNA to be Cy3 fluorescently imaged within very short lapse of time. The obtaining fluorescence signal reflects the real incorporated site of analogue replicating DNA with a very fine signal resolution. Combined with the beads loading method and drug-induced PCC, dynamic study of chromosome condensation, involving DNA replication, has been realized (Gotoh, 2007).

    Chemicals and Instruments

  • Calyculin A to induce PCC in interphase nuclei; purchased from Wako Chemicals (Osaka, Japan), dissolved in 100% DMSO, 100 μM of stock solution was stored at -20°C.
  • Cy3- or Cy5-dUTP or other fluorochrome conjugated dUTP for labelling replicating DNA. Fluorochrome choice is strictly dependent on the light source (laser) equipped on the microscope available in the individual institute. BrdU (Bromo-deoxy-Uridine) is commonly used for labeling replicating DNA and gives substantial high quality signals. But combined to laser confocal microscope, Cy3-dUTP gives much more fine signals.
  • Glass beads for beads loading methods. Various particle size and various surface treatment glass beads are provided from the company. DNA labeling efficiency using beads loading method may be varies in different cell lines, cell conditions, beads size and surface treatment. The optimum choice of beads for individual cell lines should be determined prior to the experiment.
  • Microscope. Confocal laser microscope is ideal for visualize dynamic chromosome coupled with DNA replication, although the conventional microscope may substantially work.

    Visualize the dynamics of chromosome structure formation coupled with DNA replication during S-phase

    Many studies, for visualizing the dynamics of chromosome condensation during cell division in mitosis, have been achieved and well documented. However, the visualizing study on the relationship between chromosome condensation and DNA replication is still limited. Several studies tried to define fairly well the replication foci distribution in interphase nuclei (Nakamura et al., 1986), but little is yet known about how replicating DNA is folded to higher order chromosomes (since chromosomes are invisible in interphase stage as they decondensed).
    To visualize the chromosome compaction dynamics coupled with DNA replication, more precisely in S-phase nucleus, the drug-induced PCC method was used (Gotoh et al., 1995; Asakawa and Gotoh, 1997; Johnson et al., 1999; Ito et al., 2002). The cells were unsynchronized because cell synchronization using DNA synthesis inhibitor such as thymidine may give some bias in DNA replication and consequently all phases of replication can be observed. Individual substage of S-phase can be easily identified by typical diagnostic appearances seen in different phases of S-PCCs (Mullinger and Johnson, 1983; Gollin et al., 1984; Hameister and Sperling, 1984; Savage et al., 1984; Gotoh et al., 1995; Gotoh and Durante, 2006). A drastic conformational change of chromosome structure formation along with the proceed of DNA replication, as shown in Fig. 1 (reproduced from Chromosoma. Gotoh, 2007; 116(5):453-462), is clearly revealed in PCCs following Cy3-dUTP loading. Cy3-dUTP loading procedure takes 10 minutes followed by 10 minutes of PCC induction and fixation (for details, see Materials and Methods in Chromosoma. Gotoh, 2007; 116(5):453-462). Accordingly, only replicated DNA in this short lapse will be fluoresced. Thus, the observed S-PCCs in the present study reflected the replication stages at most 20 minutes before the cell fixation. (i) In early S-phase, PCCs showed a cloudy spreading mass of thin fibres like a 'nebula', where numerous fine granular foci homogeneously distributed on overall the fibres (Fig. 1I), showing 'beads on a string' or 'particles on a string': these structures are observed under an electron microscope (Olins and Olins, 1974; Thoma et al., 1979). (ii) In the middle of S-phase, typical 'pulverized' PCCs were recognized; the size of foci was increased while the number of foci, unevenly distributed on chromosomes, was decreased. As shown in Fig. 1J, the foci become brighter. (iii) In the late S-phase, chromosomes were mostly condensed like mitotic chromosomes. Cy3-dUTP incorporated regions were recognized as band arrays inserted in the condensed chromosome (Fig. 1K, indicated by arrows). The similar appearance of replication foci along longitudinally on chromosomes were previously reported on metaphase of kangaroo-rat kidney PtK1 cells (Ma et al., 1998). The size of foci is still up and their number is still down to the point that they could be easily scored. (iv) In the very late S-phase, the number of foci is further reduced and predominantly they are localized at centromeric or telomeric regions (Fig. 1L, indicated by arrows). These regions are actually known as satellite heterochromatic DNA regions where DNA replicates at very late S (O'Keefe et al., 1992).

     

    Figure 1: (1) DNA replication regions on prematurely condensed chromosomes (PCCs) of different substages of S-phase. Ten minutes after Cy3-dUTP loading, cells were condensed prematurely using 50 nM of calyculin A (Gotoh et al., 1995). From left to right column, (A,B,C) early S-phase PCCs, (D,E,F) middle S-PCCs, (G,H,I) late S-PCCs and (J,K,L) very late S-PCCs. (A,D,G,J) DAPI counterstained DNA, (B,E,H,K) Cy3-dUTP labelled DNA replication region and (C,F,I,L) Merged image of DAPI and Cy3. (L) Centromeric region (arrow) or telomeric region (arrowhead) replicates in very-late S-phase are indicated. (I,L) Late S- and very late S-PCCs already condensed like as mitotic chromosomes, but these PCCs were actually S-phase chromosomes because they incorporated Cy3-dUTP. G2/M chromosomes are easily distinguished from late or very late S chromosomes as G2/M chromosomes do not incorporate Cy3-dUTP (data not shown). Inset in (C) is higher magnification of the boxed portion. Scale bar, 10 μm. (2) DNA replication regions seen on prominent fibre of PCCs. (M) early-S-phase and (N) middle S-phase. Replication foci are clearly seen as 'beads on a string' structure, some of these are indicated by arrowhead. Scale bar, 10 μm. (Figure reproduced from Figure 2 of Chromosoma 2007; 116(5):453-462. By Gotoh).

    Chromosome condensation/compaction coupled with DNA replication

    In the present review, the dynamics of chromosomal conformation change, which is tightly coupled with DNA replication during S-phase, was clearly seen on PCCs of different sub S-phase using drug-induced PCC method (Gotoh and Durante, 2006) and on Cy3-dUTP direct labeling method (McNeil and Warder, 1987). Drug-induced PCC would be, therefore, a useful tool that provides new insights of the dynamics of chromosome formation and DNA replication.
    As described in the previous section, number of accumulated evidences suggested the role of DNA replication in chromosome condensation/compaction (Pflumm, 2002). As previously reported, evidence and results of this study show that: (i) The different appearance of condensation in different sub-phase of S-PCCs is thought to be depended on the different degrees of chromosome conformation at the time of PCC induction (Johnson and Rao, 1970; Rao, 1977; Rao et al., 1977). In the late or very late S phase, particularly, chromosome conformation already changes like mitotic chromosomes (Fig. 1F). (ii) Chromosomes condense asynchronous and the different degree of condensation depend on the time of chromatin replication (Kuroiwa, 1971). (iii) Chromosomes are not fully diffused nor nonrandomely positioned in the nucleus, but are separately compartmentalized in interphase nuclei (Cremer et al., 1993; Ferreira et al., 1997; Berezney et al., 2000). These chromosomes, occupying the 'territory', do not intermingle (Hadlaczky et al., 1986; Cremer et al., 1993; Swedlow and Hirano, 2003; Cremer et al., 2006; Heard and Bickmore, 2007). (iv) Late replication foci were prealigned during interphase. They moved subtly to generate recognizable chromosomes presumably due to shortening of the longitudinal chromosome axis (Manders et al., 1999). (v) The gross structure of an interphase chromosome territories is directly related to that of the prophase chromosomes (Manders et al., 1999). (vi) The structure of mitotic chromosomes and the nuclear chromosome territories are closely related (Manders et al., 1999) and the different bands of mitotic chromosomes are presented as distinct domains regarded subchromosomal foci within chromosome territories (Zink et al., 1999). (vii) During the cell cycling, the global chromosome territories are conserved. Although some conflicts still remains, several studies reported that chromosome territories are transmitted through mitosis (Manders et al., 1999; Gerlich et al., 2003; Gerlich and Ellenberg, 2003) whereas others reported that positional relations of chromosome territories are lost either at mitosis (Walter et al., 2003) or at early G1 (Essers et al., 2005). (viii) The spatio-temporal organization of DNA replication is determined by the specific nuclear order of these stable chromosomal units (Sadoni et al., 2004). (ix) Chromatin domains with the dimension of replication foci may be fundamental units of chromosomal architecture (Berezney et al., 2000). (x) DNA replication occurs at fixed sites and replicated DNA move through replication center (Berezney and Coffey, 1975; Pardoll et al., 1980; Hozak et al., 1993). (xi) DNA replication contributes to a longitudinal contraction of the chromosome axis (Hearst et al., 1998). (xii) Functional replication origins are a critical requirement for longitudinal condensation of the chromosome axis (Pflumm and Botchan, 2001). The results presented in this review and previous findings strongly suggest that DNA replication, nuclear organization and chromosome condensation are mutually integrated to construct a higher ordered structure of eukaryote chromosomes.

    A hypothetical chromosome compaction model coupled with DNA replication

    Number of models for eukaryote chromosome architecture have been proposed (Marsden and Laemmli, 1979; Woodcock et al., 1984; Woodcock and Dimitrov, 2001; Swedlow and Hirano, 2003; Kireeva et al., 2004), but they are controversial and many aspects are still unclear. In addition, these models do not take account of the involvement of DNA replication/transcription in chromosome packaging. DNA/RNA polymerase are known to be tightly immobilized to the replication/transcription factories (Cook, 1999; Frouin et al., 2003). In the proposed model, DNA polymerase is thought to be a 'reel in DNA template and extrude replicated DNA' (Hozak et al., 1996; Cook, 1999) rather than an enzyme track along DNA template, which is proposed in many conventional models. In the context of Cook's model, some kinds of mechanical tension force should be generated in the DNA template along with DNA replication goes on because the factory is not freely suspended in the nucleus but attached to nucleoskeleton. Consequently, this force may pull and aggregate the replication foci of both sides as to release the tension in DNA strands, which may result in the formation of the chromosomes as seen in mitosis. Based on the above mechanism and the observed findings obtained from chromosome structure dynamics coupled with DNA replication, Fig. 2 shows a hypothetical model for the relationship between DNA replication and chromosomal conformation changes, and it shows too how the interphase chromatin is constructed into chromosomes (Figure reproduced from Chromosoma. Gotoh, 2007; 116(5): 453-462). During the S-phase, chromosomal conformation changes and the chromosome formation would be mostly completed at the end of DNA replication (Fig. 2A,B,C). From G2 to prophase, chromosomes are still more elastic, less condensed, folded only several times and prealigned in interphase nuclei (Manders et al., 1999). At these phases, the chromosomes would be observed as chromosome territories (Cremer et al., 1993; Berezney et al., 2000) (Fig. 2D). Entering in mitosis, these chromosomes would condense even more as shortening the longitudinal axis to form solid and rod shape appearance of recognizable mitotic chromosomes (Manders et al., 1999) (Fig. 2E).

    Figure 2: A hypothetical two-dimensional model for chromosome conformational change involving DNA replication based on the models proposed by Cook (Cook, 1995) or Pflumm (Pflumm, 2002). (A) Early S-phase. DNA replication starts at multiple origins and proceeds bi-directionally. Early S-PCCs are seen as 'beads on a string' appearance. (B) Middle S-phase. As DNA replication proceeds, replicated DNA pass through replication factory and some tension are generated. The generated tension may pull back the replication factories close together so as to release the tension. Replication factories may in turn fuse together and chromosomes compact. Middle S-PCCs are seen as well known 'pulverized chromosomes' appearance. (C) Late S-phase. Most of DNA finished replication and conformation was changed. Late S-PCCs are seen as 'tandem band arrayed structured chromosomes' like as mitotic chromosomes. (D) G2 to prophase. After finishing of DNA replication, chromosome conformation changed like as mitotic chromosomes, but still so elastic that packed in nucleus. Before fixation, each chromosome occupies individual chromosome territory (CT) in interphase nucleus, thus observed as compartment regions (colorized). (E) Mitosis. After prophase, chromosomes further shortening in longitudinal axis of chromosomes, consequently a straight rod shaped recognizable chromosome formed as usually seen by cytologists under a microscope. For simplicity, the model is shown as two-dimensional and the scaling is arbitrary. The model intends not to depict actual events of chromosome conformation change but to help imagine how DNA replication is involved in chromosomal conformation. As the real chromosomes condense as three-dimensionally, other elements such as coiling and helical winding should be considered together to construct a stereoscopic hierarchical structure of eukaryote chromosomes (Woodcock and Dimitrov, 2001; Swedlow and Hirano, 2003). (Figure reproduced from Figure 3 of Chromosoma 2007; 116(5):453-462. By Gotoh).

    Summary and Conclusion

    A basic and principle question of cell biology is: how DNA folds to chromosome? Numbers of evidence have suggested the involvement of DNA replication in chromosome structure formation. To visualize the dynamics of chromosome structure formation coupled with DNA replication, Cy3-dUTP direct-labeled active replicating DNA was observed in prematurely condensed chromosomes (PCCs) utilized with drug-induced premature chromosome condensation technique, which facilitates the visualization of interphase chromatin as well as the condensed chromosome form. S-phase PCCs revealed clearly the drastic dynamic transition of chromosome formation during S-phase along with the progress of DNA replication: from a 'cloudy nebula' structure in early S-phase to numerous number of 'beads on a string' in middle S-phase and finally to 'striped arrays of banding structured chromosome' in the late S-phase as usual observed in mitotic chromosomes. The drug-induced PCC is clearly provided a new insight that the eukaryote DNA replication is tightly coupled with the dynamics of chromosome condensation/compaction for the construction of eukaryote higher ordered chromosome structure. Based on these findings, a hypothetical model for chromosome compaction involved the role of DNA replication is proposed. In this model, conformational change is simply illustrated as two-dimensional but the real architecture is a three-dimensionally chromosome constructs, with much more complex fashion. It is mostly unclear how DNA replication/transcription conducts to make up a three-dimensional hierarchical structure of chromosomes coupled with twisting/folding/winding or other factors. It should be a most principle challenge in cell science.

    Bibliography

    Mammalian cell fusion: induction of premature chromosome condensation in interphase nuclei.
    Johnson RT, Rao PN.
    Nature. 1970 May 23;226(5247):717-22.
    PMID 5443247
     
    Mammalian cell fusion. 3. A HeLa cell inducer of premature chromosome condensation active in cells from a variety of animal species.
    Johnson RT, Rao PN, Hughes HD.
    J Cell Physiol. 1970 Oct;76(2):151-7.
    PMID 5533542
     
    Mammalian cell fusion: studies on the regulation of DNA synthesis and mitosis.
    Rao PN, Johnson RT.
    Nature. 1970 Jan 10;225(5228):159-64.
    PMID 5409962
     
    Asynchronous condensation of chromosomes from early prophase to late prophase as revealed by electron microscopic autoradiography.
    Kuroiwa T.
    Exp Cell Res. 1971 Nov;69(1):97-105.
    PMID 5124493
     
    Localization of newly-synthesized DNA in a mammalian cell as visualized by high resolution autoradiography.
    Fakan S, Hancock R.
    Exp Cell Res. 1974 Jan;83(1):95-102.
    PMID 4130365
     
    A cytostatic factor in amphibian oocytes: its extraction and partial characterization.
    Masui Y.
    J Exp Zool. 1974 Jan;187(1):141-7.
    PMID 4543897
     
    Spheroid chromatin units (v bodies).
    Olins AL, Olins DE.
    Science. 1974 Jan 25;183(4122):330-2.
    PMID 4128918
     
    The phenomenon of premature chromosome condensation: its relevance to basic and applied research.
    Sperling K, Rao PN.
    Humangenetik. 1974;23(4):235-58.
    PMID 4138742
     
    Nuclear protein matrix: association with newly synthesized DNA.
    Berezney R, Coffey DS.
    Science. 1975 Jul 25;189(4199):291-3.
    PMID 1145202
     
    Eukaryotic chromosome replication.
    Edenberg HJ, Huberman JA.
    Annu Rev Genet. 1975;9:245-84. (REVIEW)
    PMID 55095
     
    Premature chromosome condensation. Conformational changes of chromatin associated with phytohemagglutinin stimulation of peripheral lymphocytes.
    Hittelman WN, Rao PN.
    Exp Cell Res. 1976 Jul;100(2):219-22.
    PMID 939249
     
    Premature chromosome condensation and the fine structure of chromosomes.
    Rao PN.
    In Molecular Structure of Human Chromosomes (ed Yunis JJ) Volume 1977. Academic Press, New York, p 205-231.
     
    Premature chromosome condensation and cell cycle analysis.
    Rao PN, Wilson B, Puck TT.
    J Cell Physiol. 1977 Apr;91(1):131-41.
    PMID 323270
     
    Eucaryotic DNA: organization of the genome for replication.
    Hand R.
    Cell. 1978 Oct;15(2):317-25.
    PMID 719745
     
    Metaphase chromosome structure: evidence for a radial loop model.
    Marsden MP, Laemmli UK.
    Cell. 1979 Aug;17(4):849-58.
    PMID 487432
     
    Involvement of histone H1 in the organization of the nucleosome and of the salt-dependent superstructures of chromatin.
    Thoma F, Koller T, Klug A.
    J Cell Biol. 1979 Nov;83(2 Pt 1):403-27.
    PMID 387806
     
    Initiation of DNA synthesis in the prematurely condensed chromosomes of G1 cells.
    Hanks SK, Rao PN.
    J Cell Biol. 1980 Oct;87(1):285-91.
    PMID 7419597
     
    Packing DNA into chromosomes.
    Mullinger AM, Johnson RT.
    J Cell Sci. 1980 Dec;46:61-86.
    PMID 7228916
     
    A fixed site of DNA replication in eucaryotic cells.
    Pardoll DM, Vogelstein B, Coffey DS.
    Cell. 1980 Feb;19(2):527-36.
    PMID 7357619
     
    Studies of mammalian chromosome replication. II. Evidence for the existence of defined chromosome replicating units.
    Lau YF, Arrighi FE.
    Chromosoma. 1981;83(5):721-41.
    PMID 7028418
     
    Units of chromosome replication and packing.
    Mullinger AM, Johnson RT.
    J Cell Sci. 1983 Nov;64:179-93.
    PMID 6662858
     
    A simple method for premature chromosome condensation induction in primary human and rodent cells using polyethylene glycol.
    Pantelias GE, Maillie HD.
    Somatic Cell Genet. 1983 Sep;9(5):533-47.
    PMID 6623312
     
    The ultrastructural organization of prematurely condensed chromosomes.
    Gollin SM, Wray W, Hanks SK, Hittelman WN, Rao PN.
    J Cell Sci Suppl. 1984;1:203-21.
    PMID 6397471
     
    Description of a chromosome replication unit in individual prematurely condensed human S-phase chromosomes.
    Hameister H, Sperling K.
    Chromosoma. 1984;90(5):389-93.
    PMID 6510116
     
    Subdivision of S-phase and its use for comparative purposes in cultured human cells.
    Savage JR, Prasad R, Papworth DG.
    J Theor Biol. 1984 Nov 21;111(2):355-67.
    PMID 6513575
     
    The higher-order structure of chromatin: evidence for a helical ribbon arrangement.
    Woodcock CL, Frado LL, Rattner JB.
    J Cell Biol. 1984 Jul;99(1 Pt 1):42-52.
    PMID 6736132
     
    Direct evidence for the non-random localization of mammalian chromosomes in the interphase nucleus.
    Hadlaczky G, Went M, Ringertz NR.
    Exp Cell Res. 1986 Nov;167(1):1-15.
    PMID 3530789
     
    Structural organizations of replicon domains during DNA synthetic phase in the mammalian nucleus.
    Nakamura H, Morita T, Sato C.
    Exp Cell Res. 1986 Aug;165(2):291-7.
    PMID 3720850
     
    Glass beads load macromolecules into living cells.
    McNeil PL, Warder E.
    J Cell Sci. 1987 Dec;88 ( Pt 5):669-78.
    PMID 2459146
     
    The Xenopus cdc2 protein is a component of MPF, a cytoplasmic regulator of mitosis.
    Dunphy WG, Brizuela L, Beach D, Newport J.
    Cell. 1988 Jul 29;54(3):423-31.
    PMID 3293802
     
    Replication occurs at discrete foci spaced throughout nuclei replicating in vitro.
    Mills AD, Blow JJ, White JG, Amos WB, Wilcock D, Laskey RA.
    J Cell Sci. 1989 Nov;94 ( Pt 3):471-7.
    PMID 2632579
     
    Mapping replicational sites in the eucaryotic cell nucleus.
    Nakayasu H, Berezney R.
    J Cell Biol. 1989 Jan;108(1):1-11.
    PMID 2910875
     
    Dynamic organization of DNA replication in mammalian cell nuclei: spatially and temporally defined replication of chromosome-specific alpha-satellite DNA sequences.
    O'Keefe RT, Henderson SC, Spector DL.
    J Cell Biol. 1992 Mar;116(5):1095-110.
    PMID 1740468
     
    Regulation of the cdc25 protein during the cell cycle in Xenopus extracts.
    Kumagai A, Dunphy WG.
    Cell. 1992 Jul 10;70(1):139-51.
    PMID 1623517
     
    Role of chromosome territories in the functional compartmentalization of the cell nucleus.
    Cremer T, Kurz A, Zirbel R, Dietzel S, Rinke B, Schrock E, Speicher MR, Mathieu U, Jauch A, Emmerich P, Scherthan H, Ried T, Cremer C, Lichter P.
    Cold Spring Harb Symp Quant Biol. 1993;58:777-92.
    PMID 7525149
     
    Visualization of replication factories attached to nucleoskeleton.
    Hozak P, Hassan AB, Jackson DA, Cook PR.
    Cell. 1993 Apr 23;73(2):361-73.
    PMID 8097433
     
    A chromomeric model for nuclear and chromosome structure.
    Cook PR.
    J Cell Sci. 1995 Sep;108 ( Pt 9):2927-35. (REVIEW)
    PMID 8537432
     
    Inhibition of protein serine/threonine phophatases directly induces premature chromosome condensation in mammalian somatic cells.
    Gotoh E, Asakawa Y, Kosaka H.
    Biomedical Research (Tokyo).1995; 16(1):63-68.
     
    Detection and evaluation of chromosomal aberrations induced by high doses of gamma-irradiation using immunogold-silver painting of prematurely condensed chromosomes.
    Gotoh E, Asakawa Y.
    Int J Radiat Biol. 1996 Nov;70(5):517-20.
    PMID 8947532
     
    The role of nuclear structure in DNA replication.
    Hozak P, Jackson DA, Cook PR.
    In Eukaryotic DNA Replication: Frontiers in Molecular Biology (ed Blow JJ) Volume 1996.Oxford University Press, Oxford, p 124-142.
     
    Dynamic behavior of DNA replication domains.
    Manders EM, Stap J, Strackee J, van Driel R, Aten JA.
    Exp Cell Res. 1996 Aug 1;226(2):328-35.
    PMID 8806436
     
    A method for detecting sister chromatid exchanges using prematurely condensed chromosomes and immunogold-silver staining.
    Asakawa Y, Gotoh E.
    Mutagenesis. 1997 May;12(3):175-7.
    PMID 9175644
     
    Spatial organization of large-scale chromatin domains in the nucleus: a magnified view of single chromosome territories.
    Ferreira J, Paolella G, Ramos C, Lamond AI.
    J Cell Biol. 1997 Dec 29;139(7):1597-610.
    PMID 9412456
     
    Activation of cdc2 protein kinase during mitosis in human cells: cell cycle-dependent phosphorylation and subunit rearrangement.
    Draetta G, Beach D.
    Cell. 1988 Jul 1;54(1):17-26.
    PMID 3289755
     
    A simple method for simultaneous interphase-metaphase chromosome analysis in biodosimetry.
    Durante M, Furusawa Y, Gotoh E.
    Int J Radiat Biol. 1998 Oct;74(4):457-62;
    PMID 9798956
     
    A simple mechanism for the avoidance of entanglement during chromosome replication.
    Hearst JE, Kauffman L, McClain WM.
    Trends Genet. 1998 Jun;14(6):244-7. (REVIEW)
    PMID 9635408
     
    Spatial and temporal dynamics of DNA replication sites in mammalian cells.
    Ma H, Samarabandu J, Devdhar RS, Acharya R, Cheng PC, Meng C, Berezney R.
    J Cell Biol. 1998 Dec 14;143(6):1415-25.
    PMID 9852140
     
    Structure and dynamics of human interphase chromosome territories in vivo.
    Zink D, Cremer T, Saffrich R, Fischer R, Trendelenburg MF, Ansorge W, Stelzer EH.
    Hum Genet. 1998 Feb;102(2):241-51.
    PMID 9521598
     
    The organization of replication and transcription.
    Cook PR.
    Science. 1999 Jun 11;284(5421):1790-5. (REVIEW)
    PMID 10364545
     
    Chromatid break rejoining and exchange aberration formation following gamma-ray exposure: analysis in G2 human fibroblasts by chemically induced premature chromosome condensation.
    Gotoh E, Kawata T, Durante M.
    Int J Radiat Biol. 1999 Sep;75(9):1129-35.
    PMID 10528921
     
    Targeting double-strand breaks to replicating DNA identifies a subpathway of DSB repair that is defective in ataxia-telangiectasia cells.
    Johnson RT, Gotoh E, Mullinger AM, Ryan AJ, Shiloh Y, Ziv Y, Squires S.
    Biochem Biophys Res Commun. 1999 Aug 2;261(2):317-25.
    PMID 10425184
     
    Direct imaging of DNA in living cells reveals the dynamics of chromosome formation.
    Manders EM, Kimura H, Cook PR.
    J Cell Biol. 1999 Mar 8;144(5):813-21.
    PMID 10085283
     
    Organization of early and late replicating DNA in human chromosome territories.
    Zink D, Bornfleth H, Visser A, Cremer C, Cremer T.
    Exp Cell Res. 1999 Feb 25;247(1):176-88.
    PMID 10047460
     
    Heterogeneity of eukaryotic replicons, replicon clusters, and replication foci.
    Berezney R, Dubey DD, Huberman JA.
    Chromosoma. 2000 Mar;108(8):471-84. (REVIEW)
    PMID 10794569
     
    Aberrant replication timing induces defective chromosome condensation in Drosophila ORC2 mutants.
    Loupart ML, Krause SA, Heck MS.
    Curr Biol. 2000 Dec 14-28;10(24):1547-56.
    PMID 11137005
     
    XCDT1 is required for the assembly of pre-replicative complexes in Xenopus laevis.
    Maiorano D, Moreau J, Mechali M.
    Nature. 2000 Apr 6;404(6778):622-5.
    PMID 10766247
     
    Nuclear lamins A and B1: different pathways of assembly during nuclear envelope formation in living cells.
    Moir RD, Yoon M, Khuon S, Goldman RD.
    J Cell Biol. 2000 Dec 11;151(6):1155-68.
    PMID 11121432
     
    The Cdt1 protein is required to license DNA for replication in fission yeast.
    Nishitani H, Lygerou Z, Nishimoto T, Nurse P.
    Nature. 2000 Apr 6;404(6778):625-8.
    PMID 10766248
     
    Aphidicolin triggers a block to replication origin firing in Xenopus egg extracts.
    Marheineke K, Hyrien O.
    J Biol Chem. 2001 May 18;276(20):17092-100.
    PMID 11279043
     
    Orc mutants arrest in metaphase with abnormally condensed chromosomes.
    Pflumm MF, Botchan MR.
    Development. 2001 May;128(9):1697-707.
    PMID 11290306
     
    Higher-order structure of chromatin and chromosomes.
    Woodcock CL, Dimitrov S.
    Curr Opin Genet Dev. 2001 Apr;11(2):130-5. (REVIEW)
    PMID 11250134
     
    DNA replication in eukaryotic cells.
    Bell SP, Dutta A.
    Annu Rev Biochem. 2002;71:333-74. (REVIEW)
    PMID 12045100
     
    Epstein-Barr virus nuclear antigen-1 is highly colocalized with interphase chromatin and its newly replicated regions in particular.
    Ito S, Gotoh E, Ozawa S, Yanagi K.
    J Gen Virol. 2002 Oct;83(Pt 10):2377-83.
    PMID 12237418
     
    The role of DNA replication in chromosome condensation.
    Pflumm MF.
    Bioessays. 2002 May;24(5):411-8. (REVIEW)
    PMID 12001264
     
    Dynamics of replication foci and nuclear matrix during S phase in Allium cepa L. cells.
    Samaniego R, de la Torre C, Moreno Diaz de la Espina S.
    Planta. 2002 Jun;215(2):195-204.
    PMID 12029468
     
    Drosophila MCM10 interacts with members of the prereplication complex and is required for proper chromosome condensation.
    Christensen TW, Tye BK.
    Mol Biol Cell. 2003 Jun;14(6):2206-15.
    PMID 12808023
     
    DNA replication: a complex matter.
    Frouin I, Montecucco A, Spadari S, Maga G.
    EMBO Rep. 2003 Jul;4(7):666-70. (REVIEW)
    PMID 12835753
     
    Global chromosome positions are transmitted through mitosis in mammalian cells.
    Gerlich D, Beaudouin J, Kalbfuss B, Daigle N, Eils R, Ellenberg J.
    Cell. 2003 Mar 21;112(6):751-64.
    PMID 12654243
     
    Dynamics of chromosome positioning during the cell cycle.
    Gerlich D, Ellenberg J.
    Curr Opin Cell Biol. 2003 Dec;15(6):664-71. (REVIEW)
    PMID 14644190
     
    Regulation of chromosome condensation and segregation.
    McHugh B, Heck MM.
    Curr Opin Genet Dev. 2003 Apr;13(2):185-90. (REVIEW)
    PMID 12672496
     
    The making of the mitotic chromosome: modern insights into classical questions.
    Swedlow JR, Hirano T.
    Mol Cell. 2003 Mar;11(3):557-69. (REVIEW)
    PMID 12667441
     
    A new cytogenetic approach for the evaluation of mutagenic potential of chemicals that induce cell cycle arrest in the G2 phase.
    Terzoudi GI, Malik SI, Pantelias GE, Margaritis K, Manola K, Makropoulos W.
    Mutagenesis. 2003 Nov;18(6):539-43.
    PMID 14614190
     
    Chromosome order in HeLa cells changes during mitosis and early G1, but is stably maintained during subsequent interphase stages.
    Walter J, Schermelleh L, Cremer M, Tashiro S, Cremer T.
    J Cell Biol. 2003 Mar 3;160(5):685-97.
    PMID 12604593
     
    Altered replication timing of the HIRA/Tuple1 locus in the DiGeorge and Velocardiofacial syndromes.
    D'Antoni S, Mattina T, Di Mare P, Federico C, Motta S, Saccone S.
    Gene. 2004 May 26;333:111-9.
    PMID 15177686
     
    Visualization of early chromosome condensation: a hierarchical folding, axial glue model of chromosome structure.
    Kireeva N, Lakonishok M, Kireev I, Hirano T, Belmont AS.
    J Cell Biol. 2004 Sep 13;166(6):775-85.
    PMID 15353545
     
    Human Orc2 localizes to centrosomes, centromeres and heterochromatin during chromosome inheritance.
    Prasanth SG, Prasanth KV, Siddiqui K, Spector DL, Stillman B.
    EMBO J. 2004 Jul 7;23(13):2651-63.
    PMID 15215892
     
    Stable chromosomal units determine the spatial and temporal organization of DNA replication.
    Sadoni N, Cardoso MC, Stelzer EH, Leonhardt H, Zink D.
    J Cell Sci. 2004 Oct 15;117(Pt 22):5353-65.
    PMID 15466893
     
    Premature condensation induces breaks at the interface of early and late replicating chromosome bands bearing common fragile sites.
    El Achkar E, Gerbault-Seureau M, Muleris M, Dutrillaux B, Debatisse M.
    Proc Natl Acad Sci U S A. 2005 Dec 13;102(50):18069-74.
    PMID 16330769
     
    Nuclear dynamics of PCNA in DNA replication and repair.
    Essers J, Theil AF, Baldeyron C, van Cappellen WA, Houtsmuller AB, Kanaar R, Vermeulen W.
    Mol Cell Biol. 2005 Nov;25(21):9350-9.
    PMID 16227586
     
    Simple biodosimetry method for cases of high-dose radiation exposure using the ratio of the longest/shortest length of Giemsa-stained drug-induced prematurely condensed chromosomes (PCC).
    Gotoh E, Tanno Y.
    Int J Radiat Biol. 2005 May;81(5):379-85.
    PMID 16076753
     
    Simple biodosimetry method for use in cases of high-dose radiation exposure that scores the chromosome number of Giemsa-stained drug-induced prematurely condensed chromosomes (PCC).
    Gotoh E, Tanno Y, Takakura K.
    Int J Radiat Biol. 2005 Jan;81(1):33-40.
    PMID 15962761
     
    Initiation of DNA replication requires the RECQL4 protein mutated in Rothmund-Thomson syndrome.
    Sangrithi MN, Bernal JA, Madine M, Philpott A, Lee J, Dunphy WG, Venkitaraman AR.
    Cell. 2005 Jun 17;121(6):887-98.
    PMID 15960976
     
    The usefulness of calyculin a for cytogenetic prenatal diagnosis.
    Srebniak MI, Trapp GG, Wawrzkiewicz AK, Kaz'mierczak W, Wiczkowski AK.
    J Histochem Cytochem. 2005 Mar;53(3):391-4.
    PMID 15750027
     
    Checkpoint abrogation in G2 compromises repair of chromosomal breaks in ataxia telangiectasia cells.
    Terzoudi GI, Manola KN, Pantelias GE, Iliakis G.
    Cancer Res. 2005 Dec 15;65(24):11292-6.
    PMID 16357135
     
    Chromosome territories--a functional nuclear landscape.
    Cremer T, Cremer M, Dietzel S, Muller S, Solovei I, Fakan S.
    Curr Opin Cell Biol. 2006 Jun;18(3):307-16. (REVIEW)
    PMID 16687245
     
    Chromosome condensation outside of mitosis: mechanisms and new tools.
    Gotoh E, Durante M.
    J Cell Physiol. 2006 Nov;209(2):297-304. (REVIEW)
    PMID 16810672
     
    Shugoshin collaborates with protein phosphatase 2A to protect cohesin.
    Kitajima TS, Sakuno T, Ishiguro K, Iemura S, Natsume T, Kawashima SA, Watanabe Y.
    Nature. 2006 May 4;441(7089):46-52.
    PMID 16541025
     
    Mitotic arrest caused by an X-ray microbeam in a single cell expressing EGFP-aurora kinase B.
    Tanno Y, Kobayashi K, Tatsuka M, Gotoh E, Takakura K.
    Radiat Prot Dosimetry. 2006;122(1-4):301-6.
    PMID 17166874
     
    Deregulation of Cdt1 induces chromosomal damage without rereplication and leads to chromosomal instability.
    Tatsumi Y, Sugimoto N, Yugawa T, Narisawa-Saito M, Kiyono T, Fujita M.
    J Cell Sci. 2006 Aug 1;119(Pt 15):3128-40.
    PMID 16835273
     
    Chromosome breakage after G2 checkpoint release.
    Deckbar D, Birraux J, Krempler A, Tchouandong L, Beucher A, Walker S, Stiff T, Jeggo P, Lobrich M.
    J Cell Biol. 2007 Mar 12;176(6):749-55.
    PMID 17353355
     
    The ins and outs of gene regulation and chromosome territory organisation.
    Heard E, Bickmore W.
    Curr Opin Cell Biol. 2007 Jun;19(3):311-6. (REVIEW)
    PMID 17467967
     
    Visualizing the dynamics of chromosome structure formation coupled with DNA replication.
    Gotoh E.
    Chromosoma. 2007 Oct;116(5):453-62.
    PMID 17503067
     
    Reduced Mcm2 expression results in severe stem/progenitor cell deficiency and cancer.
    Pruitt SC, Bailey KJ, Freeland A
    Stem Cells. 2007 Dec;25(12):3121-32.
    PMID 17717065
     
    A viable allele of Mcm4 causes chromosome instability and mammary adenocarcinomas in mice.
    Shima N, Alcaraz A, Liachko I, Buske TR, Andrews CA, Munroe RJ, Hartford SA, Tye BK, Schimenti JC.
    Nat Genet. 2007 Jan;39(1):93-8.
    PMID 17143284
     
    ATM and Artemis promote homologous recombination of radiation-induced DNA double-strand breaks in G2.
    Beucher A, Birraux J, Tchouandong L, Barton O, Shibata A, Conrad S, Goodarzi AA, Krempler A, Jeggo PA, Lobrich M.
    EMBO J. 2009 Nov 4;28(21):3413-27.
    PMID 19779458
     
    Plk1 self-organization and priming phosphorylation of HsCYK-4 at the spindle midzone regulate the onset of division in human cells.
    Burkard ME, Maciejowski J, Rodriguez-Bravo V, Repka M, Lowery DM, Clauser KR, Zhang C, Shokat KM, Carr SA, Yaffe MB, Jallepalli PV.
    PLoS Biol. 2009 May 5;7(5):e1000111.
    PMID 19468302
     
    Interaction between Poly(ADP-ribose) and NuMA contributes to mitotic spindle pole assembly.
    Chang P, Coughlin M, Mitchison TJ.
    Mol Biol Cell. 2009 Nov;20(21):4575-85.
    PMID 19759176
     
    NuMA is required for proper spindle assembly and chromosome alignment in prometaphase.
    Haren L, Gnadt N, Wright M, Merdes A.
    BMC Res Notes. 2009 Apr 28;2:64.
    PMID 19400937
     
    Drug-induced premature chromosome condensation (PCC) protocols: cytogenetic approaches in mitotic chromosome and interphase chromatin.
    Gotoh E.
    Methods Mol Biol. 2009;523:83-92.
    PMID 19381920
     
    Chromatin dynamics is correlated with replication timing.
    Pliss A, Malyavantham K, Bhattacharya S, Zeitz M, Berezney R.
    Chromosoma. 2009 Aug;118(4):459-70.
    PMID 19296120
     
    Requirements for NuMA in maintenance and establishment of mammalian spindle poles.
    Silk AD, Holland AJ, Cleveland DW.
    J Cell Biol. 2009 Mar 9;184(5):677-90.
    PMID 19255246
     
    Polo-like kinase 1 directs assembly of the HsCyk-4 RhoGAP/Ect2 RhoGEF complex to initiate cleavage furrow formation.
    Wolfe BA, Takaki T, Petronczki M, Glotzer M.
    PLoS Biol. 2009 May 5;7(5):e1000110.
    PMID 19468300
     
    Cytokinesis and cancer: Polo loves ROCK'n' Rho(A).
    Li J, Wang J, Jiao H, Liao J, Xu X.
    J Genet Genomics. 2010 Mar;37(3):159-72. (REVIEW)
    PMID 20347825
     
    Eukaryotic chromosome DNA replication: where, when, and how?
    Masai H, Matsumoto S, You Z, Yoshizawa-Sugata N, Oda M.
    Annu Rev Biochem. 2010;79:89-130. (REVIEW)
    PMID 20373915
     
    A role for Cdc48/p97 and Aurora B in controlling chromatin condensation during exit from mitosis.
    Meyer H, Drozdowska A, Dobrynin G.
    Biochem Cell Biol. 2010 Feb;88(1):23-8. (REVIEW)
    PMID 20130676
     
    Phosphorylation of mammalian Sgo2 by Aurora B recruits PP2A and MCAK to centromeres.
    Tanno Y, Kitajima TS, Honda T, Ando Y, Ishiguro K, Watanabe Y.
    Genes Dev. 2010 Oct 1;24(19):2169-79.
    PMID 20889715
     
    A specific form of phospho protein phosphatase 2 regulates anaphase-promoting complex/cyclosome association with spindle poles.
    Torres JZ, Ban KH, Jackson PK.
    Mol Biol Cell. 2010 Mar;21(6):897-904.
    PMID 20089842
     
    Phosphorylation of the CPC by Cdk1 promotes chromosome bi-orientation.
    Tsukahara T, Tanno Y, Watanabe Y.
    Nature. 2010 Oct 7;467(7316):719-23.
    PMID 20739936
     
    Loss of Rb proteins causes genomic instability in the absence of mitogenic signaling.
    van Harn T, Foijer F, van Vugt M, Banerjee R, Yang F, Oostra A, Joenje H, te Riele H.
    Genes Dev. 2010 Jul 1;24(13):1377-88.
    PMID 20551164
     
    Molecular Biology of The Cell.
    Alberts B, Bray D, Lewis J, Raff M, Roberts K, Watson JD.
    Garland Publishing Inc. New York 1219 pp.
     
    Written2011-01Eisuke Gotoh
    of Genetic Resources, National Institute of Infectious Diseases Japan 1-23-1, Toyama, Shin-juku-ku, Tokyo, 162-8640, Japan; Department of Radiology, Jikei University of School of Medicine, 3-25-8, Nishi-Simbashi, Minato-ku, Tokyo, 116, Japan

    Citation

    This paper should be referenced as such :
    Gotoh, E
    Visualize Dynamic Chromosome
    Atlas Genet Cytogenet Oncol Haematol. 2011;15(9):777-786.
    Free journal version : [ pdf ]   [ DOI ]
    On line version : http://AtlasGeneticsOncology.org/Deep/VisuDynChID20093.htm

    © Atlas of Genetics and Cytogenetics in Oncology and Haematology
    indexed on : Tue Mar 14 13:58:17 CET 2017


    Home   Genes    Leukemias    Solid Tumours    Cancer-Prone    Deep Insight    Case Reports    Journals   Portal    Teaching   

    X Y 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 NA

    For comments and suggestions or contributions, please contact us

    jlhuret@AtlasGeneticsOncology.org.