TOP2A

DNA topoisomerase 2-alpha is an enzyme that in humans is encoded by the TOP2A gene.

TOP2A
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1ZXM, 1ZXN, 4FM9, 4R1F
Identifiers
Aliases	TOP2A, TOP2, TP2A, topoisomerase (DNA) II alpha, DNA topoisomerase II alpha
External IDs	OMIM: 126430 MGI: 98790 HomoloGene: 830 GeneCards: TOP2A
Gene location (Human) Chr. Chromosome 17 (human)[1] Band 17q21.2 Start 40,388,525 bp[1] End 40,417,896 bp[1]
Gene location (Mouse) Chr. Chromosome 11 (mouse)[2] Band 11 D|11 62.91 cM Start 98,992,943 bp[2] End 99,024,189 bp[2]
Gene ontology Molecular function • DNA binding • nucleotide binding • DNA-dependent ATPase activity • protein homodimerization activity • histone deacetylase binding • chromatin binding • isomerase activity • metal ion binding • DNA topoisomerase activity • protein C-terminus binding • ubiquitin binding • GO:0001948 protein binding • drug binding • protein heterodimerization activity • enzyme binding • ATP binding • protein kinase C binding • magnesium ion binding • DNA binding, bending • RNA binding • GO:0003918 DNA topoisomerase type II (double strand cut, ATP-hydrolyzing) activity Cellular component • cytoplasm • DNA topoisomerase complex (ATP-hydrolyzing) • nucleoplasm • nuclear chromosome • nucleolus • centriole • condensed chromosome • cell nucleus • viral integration complex • macromolecular complex • ribonucleoprotein Biological process • resolution of meiotic recombination intermediates • apoptotic chromosome condensation • embryonic cleavage • rhythmic process • chromosome segregation • DNA metabolic process • protein sumoylation • cellular response to DNA damage stimulus • DNA ligation • chromosome condensation • regulation of circadian rhythm • hematopoietic progenitor cell differentiation • positive regulation of apoptotic process • mitotic DNA integrity checkpoint • positive regulation of viral genome replication • positive regulation of single stranded viral RNA replication via double stranded DNA intermediate • sister chromatid segregation • positive regulation of transcription from RNA polymerase II promoter • DNA topological change • negative regulation of DNA duplex unwinding • female meiotic nuclear division Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	7153	21973
Ensembl	ENSG00000131747	ENSMUSG00000020914
UniProt	P11388	Q01320
RefSeq (mRNA)	NM_001067	NM_011623
RefSeq (protein)	NP_001058	NP_035753
Location (UCSC)	Chr 17: 40.39 – 40.42 Mb	Chr 11: 98.99 – 99.02 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

This gene encodes a DNA topoisomerase, an enzyme that controls and alters the topologic states of DNA during transcription. This nuclear enzyme is involved in processes such as chromosome condensation, chromatid separation, and the relief of torsional stress that occurs during DNA transcription and replication. It catalyzes the transient breaking and rejoining of two strands of duplex DNA which allows the strands to pass through one another, thus altering the topology of DNA. Two forms of this enzyme exist as likely products of a gene duplication event. The gene encoding this form, alpha, is localized to chromosome 17 and the beta gene is localized to chromosome 3. The gene encoding this enzyme functions as the target for several anticancer agents and a variety of mutations in this gene have been associated with the development of drug resistance. Reduced activity of this enzyme may also play a role in ataxia-telangiectasia.[5]

Interactions

TOP2A has been shown to interact with HDAC1,[6][7] CDC5L,[8] Small ubiquitin-related modifier 1[9] and P53.[10]

See also

• Topoisomerase II
• TOP2B - Topoisomerase II beta
• Gene duplication
• Ataxia-telangiectasia

References

1. GRCh38: Ensembl release 89: ENSG00000131747 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000020914 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. "Entrez Gene: TOP2A topoisomerase (DNA) II alpha 170kDa".
6. Tsai, S C; Valkov N; Yang W M; Gump J; Sullivan D; Seto E (November 2000). "Histone deacetylase interacts directly with DNA topoisomerase II". Nat. Genet. UNITED STATES. 26 (3): 349–53. doi:10.1038/81671. ISSN 1061-4036. PMID 11062478. S2CID 19301396.
7. Johnson, C A; Padget K; Austin C A; Turner B M (February 2001). "Deacetylase activity associates with topoisomerase II and is necessary for etoposide-induced apoptosis". J. Biol. Chem. United States. 276 (7): 4539–42. doi:10.1074/jbc.C000824200. ISSN 0021-9258. PMID 11136718.
8. Ajuh, P; Kuster B; Panov K; Zomerdijk J C; Mann M; Lamond A I (Dec 2000). "Functional analysis of the human CDC5L complex and identification of its components by mass spectrometry". EMBO J. ENGLAND. 19 (23): 6569–81. doi:10.1093/emboj/19.23.6569. ISSN 0261-4189. PMC 305846. PMID 11101529.
9. Mao, Y; Desai S D; Liu L F (August 2000). "SUMO-1 conjugation to human DNA topoisomerase II isozymes". J. Biol. Chem. UNITED STATES. 275 (34): 26066–73. doi:10.1074/jbc.M001831200. ISSN 0021-9258. PMID 10862613.
10. Cowell, I G; Okorokov A L; Cutts S A; Padget K; Bell M; Milner J; Austin C A (February 2000). "Human topoisomerase IIalpha and IIbeta interact with the C-terminal region of p53". Exp. Cell Res. UNITED STATES. 255 (1): 86–94. doi:10.1006/excr.1999.4772. ISSN 0014-4827. PMID 10666337.

Further reading

• Watt PM, Hickson ID (1994). "Structure and function of type II DNA topoisomerases". Biochem. J. 303 (3): 681–95. doi:10.1042/bj3030681. PMC 1137600. PMID 7980433.
• Bronner C, Hopfner R, Mousli M (2002). "Transcriptional regulation of the human topoisomerase IIalpha gene". Anticancer Res. 22 (2A): 605–12. PMID 12014628.
• Järvinen TA, Liu ET (2004). "Topoisomerase IIalpha gene (TOP2A) amplification and deletion in cancer--more common than anticipated". Cytopathology. 14 (6): 309–13. doi:10.1046/j.0956-5507.2003.00105.x. PMID 14632727. S2CID 29586255.