TOP1 (topoisomerase (DNA) 1)

Identity

Hugo	TOP1
Location	20q12-q13.1
Local_order	centromer to telomer

DNA/RNA

Note	The sequence is split into 21 exons over 85kbp. Introns are 0.2-30 kbp in size.
	The star denotes intron 7 where chromosome translocation occurs.
Description	21 exons with 20 introns
Transcription	3.8 kb (single band)
Pseudogene	2 pseudogenes. TOP1P1 on chromosome 1q23-q24, and TOP1P2 on chromosome 22q12-q13.1.

Protein

	The arrow indicates the breaking point of translocation, and the star denotes the sites of point mutation.

Note	type I DNA topoisomerase, EC (5.99.1.2)
Description	765 amino acids, about 100kDa; contains NLS in the N-term, a core domain which recognizes its binding sequences, a link domain which connects the core and catalytic domains, and the catalytic domain in the C-term.
Expression	Ubiquitous. The expression level is up-regulated along with cell proliferation signals.
Localisation	Nucleus
Function	TOP1 catalyzes the breaking and rejoining of single DNA strand.
Homology	The core and catalytic domains are conserved between the human and S.cerevisiae enzyme.

Mutations

Somatic

Translocation of chromosome t(11;20)(p15;q12) has been reported in hematological malignancies (see below). Point mutations with amino acid substitution in the catalytic domain have been implicated in irinotecan-resistance.

Implicated in

Entity	t(11;20)(p15;q12)
Disease	de novo acute myeloid leukemia, acute monocytic leukemia, therapy-related myelodysplastic syndrome/leukemia(t-MDS/AML)
Prognosis	poor (?)
Hybrid/Mutated Gene	NUP98/TOP1
Oncogenesis	NUP98-TOP1 fusion protein has been proved to have leukemogenic activities independent of topoisomerase activity.

Breakpoints

	The breakpoints locate in intron 7, causing the fusion protein to lack the N-terminal 169 amino acids.The breakpoints locate in the repetitive elements or close to them which exist in intron 7 of TOP1 gene.

To be noted

Point mutations W736stop and G737S were detected in lung non-small cell carcinoma. The significance of mutations in catalytic domain has been suspected to be relevant to susceptibility to irinotecan.

External links

	Nomenclature
Hugo	TOP1
GDB	TOP1
Entrez_Gene	TOP1  7150  topoisomerase (DNA) I
	Cards
Atlas	TOP1ID320ch20q11
GeneCards	TOP1
Ensembl	TOP1 [Search_View]   ENSG00000198900 [Gene_View]
Genatlas	TOP1
GeneLynx	TOP1
eGenome	TOP1
euGene	7150
	Genomic and cartography
GoldenPath	TOP1  -     chr20:39090876-39186538 +  20q12-q13.1   [Description]    (hg18-Mar_2006)
Ensembl	TOP1 - 20q12-q13.1 [CytoView]
NCBI	Mapview
OMIM	Disease map [OMIM]
HomoloGene	TOP1
	Gene and transcription
Genbank	AK225095 [ ENTREZ ]
Genbank	AK292943 [ ENTREZ ]
Genbank	BC000943 [ ENTREZ ]
Genbank	BC004475 [ ENTREZ ]
Genbank	BC039009 [ ENTREZ ]
RefSeq	NM_003286 [ SRS ]    NM_003286 [ ENTREZ ]
RefSeq	AC_000063 [ SRS ]    AC_000063 [ ENTREZ ]
RefSeq	NC_000020 [ SRS ]    NC_000020 [ ENTREZ ]
RefSeq	NT_011362 [ SRS ]    NT_011362 [ ENTREZ ]
RefSeq	NW_927339 [ SRS ]    NW_927339 [ ENTREZ ]
AceView	TOP1 AceView - NCBI
Unigene	Hs.592136 [ SRS ]    Hs.592136 [ NCBI ]     HS592136 [ spliceNest ]
Fast-db	11362 (alternative variants)
	Protein : pattern, domain, 3D structure
SwissProt	P11387 [ SRS]    P11387 [ EXPASY ]     P11387 [ INTERPRO ]
Prosite	PS00176 TOPOISOMERASE_I_EUK [ SRS ]    PS00176 TOPOISOMERASE_I_EUK [ Expasy ]
Interpro	IPR001631 TopoI_C [ SRS ]    IPR001631 TopoI_C [ EBI ]
Interpro	IPR013499 TopoI_C_euk [ SRS ]    IPR013499 TopoI_C_euk [ EBI ]
Interpro	IPR014711 TopoI_cat_a-hlx-sub_euk [ SRS ]    IPR014711 TopoI_cat_a-hlx-sub_euk [ EBI ]
Interpro	IPR014727 TopoI_cat_a/b-sub_euk [ SRS ]    IPR014727 TopoI_cat_a/b-sub_euk [ EBI ]
Interpro	IPR013500 TopoI_cat_euk [ SRS ]    IPR013500 TopoI_cat_euk [ EBI ]
Interpro	IPR013030 TopoI_DNA-bd_mixed-a/b_euk [ SRS ]    IPR013030 TopoI_DNA-bd_mixed-a/b_euk [ EBI ]
Interpro	IPR008336 TopoI_DNA_bd_euk [ SRS ]    IPR008336 TopoI_DNA_bd_euk [ EBI ]
CluSTr	P11387
Pfam	PF01028 Topoisom_I [ SRS ]    PF01028 Topoisom_I [ Sanger ]    pfam01028 [ NCBI-CDD ]
Pfam	PF02919 Topoisom_I_N [ SRS ]    PF02919 Topoisom_I_N [ Sanger ]    pfam02919 [ NCBI-CDD ]
Smart	SM00435 TOPEUc [EMBL]
Blocks	P11387
PDB	1A31 [ SRS ]    1A31 [ PdbSum ],   1A31 [ IMB ]   1A31 [ RSDB ]
PDB	1A35 [ SRS ]    1A35 [ PdbSum ],   1A35 [ IMB ]   1A35 [ RSDB ]
PDB	1A36 [ SRS ]    1A36 [ PdbSum ],   1A36 [ IMB ]   1A36 [ RSDB ]
PDB	1EJ9 [ SRS ]    1EJ9 [ PdbSum ],   1EJ9 [ IMB ]   1EJ9 [ RSDB ]
PDB	1K4S [ SRS ]    1K4S [ PdbSum ],   1K4S [ IMB ]   1K4S [ RSDB ]
PDB	1K4T [ SRS ]    1K4T [ PdbSum ],   1K4T [ IMB ]   1K4T [ RSDB ]
PDB	1LPQ [ SRS ]    1LPQ [ PdbSum ],   1LPQ [ IMB ]   1LPQ [ RSDB ]
PDB	1NH3 [ SRS ]    1NH3 [ PdbSum ],   1NH3 [ IMB ]   1NH3 [ RSDB ]
PDB	1R49 [ SRS ]    1R49 [ PdbSum ],   1R49 [ IMB ]   1R49 [ RSDB ]
PDB	1RR8 [ SRS ]    1RR8 [ PdbSum ],   1RR8 [ IMB ]   1RR8 [ RSDB ]
PDB	1RRJ [ SRS ]    1RRJ [ PdbSum ],   1RRJ [ IMB ]   1RRJ [ RSDB ]
PDB	1SC7 [ SRS ]    1SC7 [ PdbSum ],   1SC7 [ IMB ]   1SC7 [ RSDB ]
PDB	1SEU [ SRS ]    1SEU [ PdbSum ],   1SEU [ IMB ]   1SEU [ RSDB ]
PDB	1T8I [ SRS ]    1T8I [ PdbSum ],   1T8I [ IMB ]   1T8I [ RSDB ]
PDB	1TL8 [ SRS ]    1TL8 [ PdbSum ],   1TL8 [ IMB ]   1TL8 [ RSDB ]
HPRD	00535
	Protein Interaction databases
DIP	P11387
IntAct	P11387
	Polymorphism : SNP, mutations, diseases
OMIM	126420    [ map ]
GENECLINICS	126420
SNP	TOP1 [dbSNP-NCBI]
SNP	NM_003286 [SNP-NCI]
SNP	TOP1 [GeneSNPs - Utah]  TOP1] [HGBASE - SRS]
HAPMAP	TOP1 [HAPMAP]
COSMIC	TOP1 [Somatic mutation (COSMIC-CGP-Sanger)]
TICdb	TOP1 [Translocation breakpoints In Cancer]
HGMD	TOP1
	General knowledge
Family Browser	TOP1 [UCSC Family Browser]
SOURCE	NM_003286
SMD	Hs.592136
SAGE	Hs.592136
Enzyme	5.99.1.2 [ Enzyme-SRS ]   5.99.1.2 [ Brenda-SRS ]   5.99.1.2 [ KEGG ]   5.99.1.2 [ WIT ]
GO	chromatin binding [Amigo]  chromatin binding
GO	DNA topoisomerase type I activity [Amigo]  DNA topoisomerase type I activity
GO	DNA topoisomerase (ATP-hydrolyzing) activity [Amigo]  DNA topoisomerase (ATP-hydrolyzing) activity
GO	protein binding [Amigo]  protein binding
GO	nucleus [Amigo]  nucleus
GO	nucleoplasm [Amigo]  nucleoplasm
GO	chromosome [Amigo]  chromosome
GO	nucleolus [Amigo]  nucleolus
GO	DNA topological change [Amigo]  DNA topological change
GO	DNA unwinding during replication [Amigo]  DNA unwinding during replication
GO	programmed cell death [Amigo]  programmed cell death
GO	phosphorylation [Amigo]  phosphorylation
GO	response to drug [Amigo]  response to drug
PubGene	TOP1
TreeFam	TOP1
CTD	7150 [Comparative ToxicoGenomics Database]
	Other databases
	Probes
Probe	TOP1 Related clones (RZPD - Berlin)
	PubMed
PubMed	112 Pubmed reference(s) in LocusLink

Bibliography

Structure of the human type I DNA topoisomerase gene.

Kunze N, Yang GC, D��lberg M, Sundarp R, Knippers R, Richter A

The Journal of biological chemistry. 1991 ; 266 (15) : 9610-9616.

PMID 1851751

The t(11;20)(p15;q11) chromosomal translocation associated with therapy-related myelodysplastic syndrome results in an NUP98-TOP1 fusion.

Ahuja HG, Felix CA, Aplan PD

Blood. 1999 ; 94 (9) : 3258-3261.

PMID 10556215

Potential role for DNA topoisomerase II poisons in the generation of t(11;20)(p15;q11) translocations.

Ahuja HG, Felix CA, Aplan PD

Genes, chromosomes & cancer. 2000 ; 29 (2) : 96-105.

PMID 10959088

Expression of NUP98/TOP1, but not of TOP1/NUP98, in a treatment-related myelodysplastic syndrome with t(10;20;11)(q24;q11;p15).

Panagopoulos I, Fioretos T, Isaksson M, Larsson G, Billstr��m R, Mitelman F, Johansson B

Genes, chromosomes & cancer. 2002 ; 34 (2) : 249-254.

PMID 11979559

Point mutations in the topoisomerase I gene in patients with non-small cell lung cancer treated with irinotecan.

Tsurutani J, Nitta T, Hirashima T, Komiya T, Uejima H, Tada H, Syunichi N, Tohda A, Fukuoka M, Nakagawa K

Lung cancer (Amsterdam, Netherlands). 2002 ; 35 (3) : 299-304.

PMID 11844605

Generation of the NUP98-TOP1 fusion transcript by the t(11;20) (p15;q11) in a case of acute monocytic leukemia.

Chen S, Xue Y, Chen Z, Guo Y, Wu Y, Pan J

Cancer genetics and cytogenetics. 2003 ; 140 (2) : 153-156.

PMID 12645654

Both NUP98/TOP1 and TOP1/NUP98 transcripts are detected in a de novo AML with t(11;20)(p15;q11).

Iwase S, Akiyama N, Sekikawa T, Saito S, Arakawa Y, Horiguchi-Yamada J, Yamada H

Genes, chromosomes & cancer. 2003 ; 38 (1) : 102-105.

PMID 12874791

NUP98-topoisomerase I acute myeloid leukemia-associated fusion gene has potent leukemogenic activities independent of an engineered catalytic site mutation.

Gurevich RM, Aplan PD, Humphries RK

Blood. 2004 ; 104 (4) : 1127-1136.

PMID 15100157

A t(11;20)(p15;q11) may identify a subset of nontherapy-related acute myelocytic leukemia.

Potenza L, Sinigaglia B, Luppi M, Morselli M, Saviola A, Ferrari A, Riva G, Zucchini P, Giacobbi F, Emilia G, Temperani P, Torelli G

Cancer genetics and cytogenetics. 2004 ; 149 (2) : 164-168.

PMID 15036893

REVIEW articles	automatic search in PubMed
Last year publications	automatic search in PubMed

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Contributor(s)

Written	12-2004	Junko Horiguchi Yamada
		Department of Oncology, Institute of DNA Medicine, The Jikei University, School of Medicine, Tokyo, Japan

Citation

This paper should be referenced as such :

Yamada JH . TOP1 (topoisomerase (DNA) 1). Atlas Genet Cytogenet Oncol Haematol. December 2004 . URL : http://AtlasGeneticsOncology.org/Genes/TOP1ID320ch20q11.html

© Atlas of Genetics and Cytogenetics in Oncology and Haematology

indexed on : Wed Jul 2 08:27:46 2008