TOP1 (topoisomerase (DNA) 1)
2004-12-01 Junko Horiguchi Yamada AffiliationDepartment of Oncology, Institute of DNA Medicine, The Jikei University, School of Medicine, Tokyo, Japan
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.
Proteins
Note
type I DNA topoisomerase, EC (5.99.1.2)
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.
Point mutations with amino acid substitution in the catalytic domain have been implicated in irinotecan-resistance.
Implicated in
Entity name
Disease
de novo acute myeloid leukemia, acute monocytic leukemia, therapy-related myelodysplastic syndrome/leukemia(t-MDS/AML)
Prognosis
poor (?)
Hybrid 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.
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 10959088 | 2000 | Potential role for DNA topoisomerase II poisons in the generation of t(11;20)(p15;q11) translocations. | Ahuja HG et al |
| 12645654 | 2003 | Generation of the NUP98-TOP1 fusion transcript by the t(11;20) (p15;q11) in a case of acute monocytic leukemia. | Chen S et al |
| 15100157 | 2004 | NUP98-topoisomerase I acute myeloid leukemia-associated fusion gene has potent leukemogenic activities independent of an engineered catalytic site mutation. | Gurevich RM et al |
| 12874791 | 2003 | Both NUP98/TOP1 and TOP1/NUP98 transcripts are detected in a de novo AML with t(11;20)(p15;q11). | Iwase S et al |
| 1851751 | 1991 | Structure of the human type I DNA topoisomerase gene. | Kunze N et al |
| 11979559 | 2002 | 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 et al |
| 15036893 | 2004 | A t(11;20)(p15;q11) may identify a subset of nontherapy-related acute myelocytic leukemia. | Potenza L et al |
| 11844605 | 2002 | Point 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 ID | Transcript ID | Uniprot |
|---|---|---|
| ENSG00000198900 | ENST00000361337 | P11387 |
Expression (GTEx)
Pathways
Protein levels (Protein atlas)
PharmGKB
| Entity ID | Name | Type | Evidence | Association | PK | PD | PMIDs |
|---|---|---|---|---|---|---|---|
| PA165110775 | SN-38 | Chemical | Pathway | associated | |||
| PA450085 | irinotecan | Chemical | ClinicalAnnotation | associated | PD | 18347181 |
References
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 38340342 | 2024 | G-quadruplexes on chromosomal DNA negatively regulates topoisomerase 1 activity. | 0 |
| 38710779 | 2024 | Levels of anti-topoisomerase I antibody correlated with short onset of cardiopulmonary involvement in Thai systemic sclerosis patients. | 0 |
| 38787953 | 2024 | Human DNA topoisomerase I poisoning causes R loop-mediated genome instability attenuated by transcription factor IIS. | 1 |
| 38340342 | 2024 | G-quadruplexes on chromosomal DNA negatively regulates topoisomerase 1 activity. | 0 |
| 38710779 | 2024 | Levels of anti-topoisomerase I antibody correlated with short onset of cardiopulmonary involvement in Thai systemic sclerosis patients. | 0 |
| 38787953 | 2024 | Human DNA topoisomerase I poisoning causes R loop-mediated genome instability attenuated by transcription factor IIS. | 1 |
| 37831776 | 2023 | Coinhibition of topoisomerase 1 and BRD4-mediated pause release selectively kills pancreatic cancer via readthrough transcription. | 3 |
| 37831776 | 2023 | Coinhibition of topoisomerase 1 and BRD4-mediated pause release selectively kills pancreatic cancer via readthrough transcription. | 3 |
| 34974222 | 2022 | TDP1 and TOP1 as targets in anticancer treatment of NSCLC: Activity and protein level in normal and tumor tissue from 150 NSCLC patients correlated to clinical data. | 3 |
| 35013228 | 2022 | Topoisomerase I (TOP1) dynamics: conformational transition from open to closed states. | 8 |
| 35140396 | 2022 | Signatures of TOP1 transcription-associated mutagenesis in cancer and germline. | 31 |
| 35687110 | 2022 | Topoisomerase 1 inhibits MYC promoter activity by inducing G-quadruplex formation. | 7 |
| 34974222 | 2022 | TDP1 and TOP1 as targets in anticancer treatment of NSCLC: Activity and protein level in normal and tumor tissue from 150 NSCLC patients correlated to clinical data. | 3 |
| 35013228 | 2022 | Topoisomerase I (TOP1) dynamics: conformational transition from open to closed states. | 8 |
| 35140396 | 2022 | Signatures of TOP1 transcription-associated mutagenesis in cancer and germline. | 31 |
Citation
Junko Horiguchi Yamada
TOP1 (topoisomerase (DNA) 1)
Atlas Genet Cytogenet Oncol Haematol. 2004-12-01
Online version: http://atlasgeneticsoncology.org/gene/320/top1
