TOP2A

Topoisomerase (DNA) II alpha
PDB rendering based on 1zxm.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1LWZ​, 1ZXM​, 1ZXN​, 4FM9​, 4R1F​
Identifiers
Symbols	TOP2A ; TOP2; TP2A
External IDs	OMIM: 126430 MGI: 98790 HomoloGene: 830 ChEMBL: 1806 GeneCards: TOP2A Gene
EC number	5.99.1.3
Gene ontology Molecular function • magnesium ion binding • DNA binding • chromatin binding • DNA topoisomerase type II (ATP-hydrolyzing) activity • protein kinase C binding • protein binding • ATP binding • protein C-terminus binding • DNA-dependent ATPase activity • drug binding • DNA binding, bending • enzyme binding • protein homodimerization activity • histone deacetylase binding • ubiquitin binding • poly(A) RNA binding • protein heterodimerization activity Cellular component • nuclear chromosome • condensed chromosome • nucleus • nucleoplasm • nucleolus • centriole • nucleoid • DNA topoisomerase complex (ATP-hydrolyzing) • viral integration complex • protein complex Biological process • mitotic cell cycle • resolution of meiotic recombination intermediates • sister chromatid segregation • hematopoietic progenitor cell differentiation • DNA topological change • DNA ligation • DNA unwinding involved in DNA replication • cellular response to DNA damage stimulus • chromosome segregation • apoptotic chromosome condensation • embryonic cleavage • regulation of circadian rhythm • 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 • positive regulation of transcription from RNA polymerase II promoter • rhythmic process 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

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

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.^[1]

Interactions

TOP2A has been shown to interact with HDAC1,^[2][3] CDC5L,^[4] Small ubiquitin-related modifier 1^[5] and P53.^[6]

References

1. "Entrez Gene: TOP2A topoisomerase (DNA) II alpha 170kDa".
2. 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.
3. 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.
4. 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.
5. 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.
6. 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. 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.