TOP1 (topoisomerase (DNA) 1)

2004-12-01 Junko Horiguchi Yamada Affiliation

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

Identity

HGNC

TOP1

LOCATION

20q12

LOCUSID

7150

ALIAS

TOPI

FUSION GENES

Show Gene Fusions

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.

Implicated in

Entity name

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 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)

100

150

Adipose - Subcutaneous

Adipose - Visceral

Adrenal Gland

Artery - Aorta

Artery - Tibial

Bladder

Brain - Amygdala

Brain - Anterior cingulate cortex

Brain - Caudate

Brain - Cerebellar Hemisphere

Brain - Cerebellum

Brain - Cortex

Brain - Frontal Cortex

Brain - Hippocampus

Brain - Hypothalamus

Brain - Nucleus accumbens

Brain - Putamen

Brain - Spinal cord

Brain - Substantia nigra

Breast - Mammary Tissue

Cells - Cultured fibroblasts

Cells - EBV - transformed lymphocytes

Cervix - Ectocervix

Cervix - Endocervix

Colon - Sigmoid

Colon - Transverse

Esophagus - Gastroesophageal Junction

Esophagus - Mucosa

Esophagus - Muscularis

Fallopian Tube

Heart - Atrial Appendage

Heart - Left Ventricle

Kidney - Cortex

Kidney - Medulla

Liver

Lung

Minor Salivary Gland

Muscle - Skeletal

Nerve - Tibial

Ovary

Pancreas

Pituitary

Prostate

Skin - Not Sun Exposed

Skin - Sun Exposed

Small Intestine - Terminal Ileum

Spleen

Stomach

Testis

Thyroid

Uterus

Vagina

Whole Blood

Pathways

Pathway	Source	External ID
Metabolism of proteins	REACTOME	R-HSA-392499
Post-translational protein modification	REACTOME	R-HSA-597592
SUMOylation	REACTOME	R-HSA-2990846
SUMO E3 ligases SUMOylate target proteins	REACTOME	R-HSA-3108232
SUMOylation of DNA replication proteins	REACTOME	R-HSA-4615885

Protein levels (Protein atlas)

Not detected

Low

Medium

High

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-(topoisomerase-(dna)-1)