TOP1 (topoisomerase (DNA) 1)

2004-12-01   Junko Horiguchi Yamada 

Department of Oncology, Institute of DNA Medicine, The Jikei University, School of Medicine, Tokyo, Japan

Identity

HGNC
LOCATION
20q12
LOCUSID
ALIAS
TOPI
FUSION GENES

DNA/RNA

Note

The sequence is split into 21 exons over 85kbp. Introns are 0.2-30 kbp in size.
Atlas Image
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.

Proteins

Note

type I DNA topoisomerase, EC (5.99.1.2)
Atlas Image
The arrow indicates the breaking point of translocation, and the star denotes the sites of point mutation.

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

Disease
de novo acute myeloid leukemia, acute monocytic leukemia, therapy-related myelodysplastic syndrome/leukemia(t-MDS/AML)
Prognosis
poor (?)
Hybrid gene
NUP98/TOP1
Atlas Image
Oncogenesis
NUP98-TOP1 fusion protein has been proved to have leukemogenic activities independent of topoisomerase activity.

Breakpoints

Atlas Image
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.

Bibliography

Pubmed IDLast YearTitleAuthors
109590882000Potential role for DNA topoisomerase II poisons in the generation of t(11;20)(p15;q11) translocations.Ahuja HG et al
126456542003Generation of the NUP98-TOP1 fusion transcript by the t(11;20) (p15;q11) in a case of acute monocytic leukemia.Chen S et al
151001572004NUP98-topoisomerase I acute myeloid leukemia-associated fusion gene has potent leukemogenic activities independent of an engineered catalytic site mutation.Gurevich RM et al
128747912003Both NUP98/TOP1 and TOP1/NUP98 transcripts are detected in a de novo AML with t(11;20)(p15;q11).Iwase S et al
18517511991Structure of the human type I DNA topoisomerase gene.Kunze N et al
119795592002Expression of NUP98/TOP1, but not of TOP1/NUP98, in a treatment-related myelodysplastic syndrome with t(10;20;11)(q24;q11;p15).Panagopoulos I et al
150368932004A t(11;20)(p15;q11) may identify a subset of nontherapy-related acute myelocytic leukemia.Potenza L et al
118446052002Point mutations in the topoisomerase I gene in patients with non-small cell lung cancer treated with irinotecan.Tsurutani J et al

Other Information

Locus ID:

NCBI: 7150
MIM: 126420
HGNC: 11986
Ensembl: ENSG00000198900

Variants:

dbSNP: 7150
ClinVar: 7150
TCGA: ENSG00000198900
COSMIC: TOP1

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000198900ENST00000361337P11387

Expression (GTEx)

0
50
100
150

Pathways

PathwaySourceExternal ID
Metabolism of proteinsREACTOMER-HSA-392499
Post-translational protein modificationREACTOMER-HSA-597592
SUMOylationREACTOMER-HSA-2990846
SUMO E3 ligases SUMOylate target proteinsREACTOMER-HSA-3108232
SUMOylation of DNA replication proteinsREACTOMER-HSA-4615885

Protein levels (Protein atlas)

Not detected
Low
Medium
High

PharmGKB

Entity IDNameTypeEvidenceAssociationPKPDPMIDs
PA165110775SN-38ChemicalPathwayassociated
PA450085irinotecanChemicalClinicalAnnotationassociatedPD18347181

References

Pubmed IDYearTitleCitations
124264032002The mechanism of topoisomerase I poisoning by a camptothecin analog.185
223750142012Tyrosyl-DNA phosphodiesterase 1 (TDP1) repairs DNA damage induced by topoisomerases I and II and base alkylation in vertebrate cells.62
158302062005Human DNA topoisomerase I: relaxation, roles, and damage control.55
270586662016RNA Polymerase II Regulates Topoisomerase 1 Activity to Favor Efficient Transcription.55
247930322014Aberrant topoisomerase-1 DNA lesions are pathogenic in neurodegenerative genome instability syndromes.54
256196912015Ligand-dependent enhancer activation regulated by topoisomerase-I activity.47
185157982008A ubiquitin-proteasome pathway for the repair of topoisomerase I-DNA covalent complexes.46
221588652012Enhanced killing of cancer cells by poly(ADP-ribose) polymerase inhibitors and topoisomerase I inhibitors reflects poisoning of both enzymes.46
301507752018The NORAD lncRNA assembles a topoisomerase complex critical for genome stability.44
252694792014ATR inhibitors VE-821 and VX-970 sensitize cancer cells to topoisomerase i inhibitors by disabling DNA replication initiation and fork elongation responses.41

Citation

Junko Horiguchi Yamada

TOP1 (topoisomerase (DNA) 1)

Atlas Genet Cytogenet Oncol Haematol. 2004-12-01

Online version: http://atlasgeneticsoncology.org/gene/320/top1