TOP2A

TOP2A
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesTOP2A, TOP2, TP2A, topoisomerase (DNA) II alpha, DNA topoisomerase II alpha, TOPIIA, TOP2alpha
External IDsOMIM: 126430; MGI: 98790; HomoloGene: 830; GeneCards: TOP2A; OMA:TOP2A - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_001067

NM_011623

RefSeq (protein)

NP_001058

NP_035753

Location (UCSC)Chr 17: 40.39 – 40.42 MbChr 11: 98.88 – 98.92 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

DNA topoisomerase IIα is a human enzyme encoded by the TOP2A gene.

Topoisomerase IIα relieves topological DNA stress during transcription, condenses chromosomes, and separates chromatids. It catalyzes the transient breaking and rejoining of two strands of duplex DNA which allows the strands to pass through one another. 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 chemotherapy agents[5] and a variety of mutations in this gene have been associated with the development of drug resistance.[citation needed] Reduced activity of this enzyme may also play a role in ataxia-telangiectasia.[6]

Interactions

TOP2A has been shown to interact with SMURF2,[7] HDAC1,[8][9] CDC5L,[10] Small ubiquitin-related modifier 1,[11] P53,[12] and TOPBP1.[13]

In other species

In Drosophila Hadlaczky et al 1988 found DNA topoisomerase II α to correlate with cell proliferation - but β did not.[14]

See also

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000131747Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000020914Ensembl, 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. ^ Deweese, J. E.; Osheroff, N. (2009-02-01). "The DNA cleavage reaction of topoisomerase II: wolf in sheep's clothing". Nucleic Acids Research. 37 (3): 738–748. doi:10.1093/nar/gkn937. ISSN 0305-1048. PMC 2647315. PMID 19042970.
  6. ^ "Entrez Gene: TOP2A topoisomerase (DNA) II alpha 170kDa".
  7. ^ Emanuelli A, Borroni AP, Apel-Sarid L, Shah PA, Ayyathan DM, Koganti P, et al. (August 2017). "Smurf2-Mediated Stabilization of DNA Topoisomerase IIα Controls Genomic Integrity". Cancer Research. 77 (16): 4217–4227. doi:10.1158/0008-5472.CAN-16-2828. PMID 28611047.
  8. ^ Tsai SC, Valkov N, Yang WM, Gump J, Sullivan D, Seto E (November 2000). "Histone deacetylase interacts directly with DNA topoisomerase II". Nature Genetics. 26 (3): 349–353. doi:10.1038/81671. PMID 11062478. S2CID 19301396.
  9. ^ Johnson CA, Padget K, Austin CA, Turner BM (February 2001). "Deacetylase activity associates with topoisomerase II and is necessary for etoposide-induced apoptosis". The Journal of Biological Chemistry. 276 (7): 4539–4542. doi:10.1074/jbc.C000824200. PMID 11136718.
  10. ^ Ajuh P, Kuster B, Panov K, Zomerdijk JC, Mann M, Lamond AI (December 2000). "Functional analysis of the human CDC5L complex and identification of its components by mass spectrometry". The EMBO Journal. 19 (23): 6569–6581. doi:10.1093/emboj/19.23.6569. PMC 305846. PMID 11101529.
  11. ^ Mao Y, Desai SD, Liu LF (August 2000). "SUMO-1 conjugation to human DNA topoisomerase II isozymes". The Journal of Biological Chemistry. 275 (34): 26066–26073. doi:10.1074/jbc.M001831200. PMID 10862613.
  12. ^ Cowell IG, Okorokov AL, Cutts SA, Padget K, Bell M, Milner J, Austin CA (February 2000). "Human topoisomerase IIalpha and IIbeta interact with the C-terminal region of p53". Experimental Cell Research. 255 (1): 86–94. doi:10.1006/excr.1999.4772. PMID 10666337.
  13. ^ Broderick, Ronan; Niedzwiedz, Wojciech (2015-08-12). "Sister chromatid decatenation: bridging the gaps in our knowledge". Cell Cycle. 14 (19): 3040–3044. doi:10.1080/15384101.2015.1078039. ISSN 1538-4101. PMC 4825568. PMID 26266709.
  14. ^ Wang JC (1996). "DNA topoisomerases". Annual Review of Biochemistry. 65 (1). Annual Reviews: 635–692. doi:10.1146/annurev.bi.65.070196.003223. PMID 8811192.

Further reading