TOP2B

DNA topoisomerase 2-beta is an enzyme that in humans is encoded by the TOP2B gene.[5][6]

TOP2B
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesTOP2B, TOPIIB, top2beta, topoisomerase (DNA) II beta, DNA topoisomerase II beta
External IDsOMIM: 126431 MGI: 98791 HomoloGene: 134711 GeneCards: TOP2B
Gene location (Human)
Chr.Chromosome 3 (human)[1]
Band3p24.2Start25,597,905 bp[1]
End25,664,907 bp[1]
RNA expression pattern
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez

7155

21974

Ensembl

ENSG00000077097

ENSMUSG00000017485

UniProt

Q02880

Q64511

RefSeq (mRNA)

NM_001068
NM_001330700

NM_009409

RefSeq (protein)

NP_001059
NP_001317629

NP_033435

Location (UCSC)Chr 3: 25.6 – 25.66 MbChr 14: 16.37 – 16.44 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Function

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, beta, is localized to chromosome 3 and the alpha form is localized to chromosome 17. The gene encoding this enzyme functions as the target for several anticancer agents, for example mitoxantrone, 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. Alternative splicing of this gene results in two transcript variants; however, the second variant has not yet been fully described.[7]

Neuronal activity

During a new learning experience, a set of genes is rapidly expressed in the brain. This induced gene expression is considered to be essential for processing the information being learned. Such genes are referred to as immediate early genes (IEGs). TOP2B activity is essential for the expression of IEGs in a type of learning experience in mice termed associative fear memory.[8] Such a learning experience appears to rapidly trigger TOP2B to induce double-strand breaks in the promoter DNA of IEG genes that function in neuroplasticity. Repair of these induced breaks is associated with DNA demethylation of IEG gene promoters allowing immediate expression of these IEG genes.[8]

Interactions of TOP2B and DNA also regulate transcription of genes that are important for development. These include genes encoding axon guidance factors and cell adhesion molecules. Specifically, TOP2B is required for lamina-specific targeting of retinal ganglion cell axons and dendrites in the zebrafish.[9]

Interactions

TOP2B has been shown to interact with:

References
  1. GRCh38: Ensembl release 89: ENSG00000077097 - Ensembl, May 2017
  2. GRCm38: Ensembl release 89: ENSMUSG00000017485 - 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. Tan KB, Dorman TE, Falls KM, Chung TD, Mirabelli CK, Crooke ST, Mao J (Jan 1992). "Topoisomerase II alpha and topoisomerase II beta genes: Characterization and mapping to human chromosomes 17 and 3, respectively". Cancer Research. 52 (1): 231–4. PMID 1309226.
  6. Jenkins JR, Ayton P, Jones T, Davies SL, Simmons DL, Harris AL, Sheer D, Hickson ID (Nov 1992). "Isolation of cDNA clones encoding the beta isozyme of human DNA topoisomerase II and localisation of the gene to chromosome 3p24". Nucleic Acids Research. 20 (21): 5587–92. doi:10.1093/nar/20.21.5587. PMC 334390. PMID 1333583.
  7. "Entrez Gene: TOP2B topoisomerase (DNA) II beta 180kDa".
  8. Li, Xiang; Marshall, Paul R.; Leighton, Laura J.; Zajaczkowski, Esmi L.; Wang, Ziqi; Madugalle, Sachithrani U.; Yin, Jiayu; Bredy, Timothy W.; Wei, Wei (2019). "The DNA Repair-Associated Protein Gadd45γ Regulates the Temporal Coding of Immediate Early Gene Expression within the Prelimbic Prefrontal Cortex and is Required for the Consolidation of Associative Fear Memory". The Journal of Neuroscience. 39 (6): 970–983. doi:10.1523/JNEUROSCI.2024-18.2018. PMC 6363930. PMID 30545945. (Erratum: PMID 30545945)
  9. Nevin, L. M.; Xiao, T.; Staub, W.; Baier, H. (2011). "Topoisomerase II is required for lamina-specific targeting of retinal ganglion cell axons and dendrites". Development. 138 (12): 2457–2465. doi:10.1242/dev.060335. PMC 3100707. PMID 21610027.
  10. Kitagawa H, Fujiki R, Yoshimura K, Mezaki Y, Uematsu Y, Matsui D, Ogawa S, Unno K, Okubo M, Tokita A, Nakagawa T, Ito T, Ishimi Y, Nagasawa H, Matsumoto T, Yanagisawa J, Kato S (Jun 2003). "RETRACTED: The Chromatin-Remodeling Complex WINAC Targets a Nuclear Receptor to Promoters and is Impaired in Williams Syndrome". Cell. 113 (7): 905–17. doi:10.1016/s0092-8674(03)00436-7. PMID 12837248.
  11. Tsai SC, Valkov N, Yang WM, Gump J, Sullivan D, Seto E (Nov 2000). "Histone deacetylase interacts directly with DNA topoisomerase II". Nature Genetics. 26 (3): 349–53. doi:10.1038/81671. PMID 11062478. S2CID 19301396.
  12. Johnson CA, Padget K, Austin CA, Turner BM (Feb 2001). "Deacetylase activity associates with topoisomerase II and is necessary for etoposide-induced apoptosis". The Journal of Biological Chemistry. 276 (7): 4539–42. doi:10.1074/jbc.C000824200. PMID 11136718.
  13. Cowell IG, Okorokov AL, Cutts SA, Padget K, Bell M, Milner J, Austin CA (Feb 2000). "Human Topoisomerase IIα and IIβ Interact with the C-Terminal Region of p53". Experimental Cell Research. 255 (1): 86–94. doi:10.1006/excr.1999.4772. PMID 10666337.
  14. Mao Y, Desai SD, Liu LF (Aug 2000). "SUMO-1 conjugation to human DNA topoisomerase II isozymes". The Journal of Biological Chemistry. 275 (34): 26066–73. doi:10.1074/jbc.M001831200. PMID 10862613.
  15. Nakano H, Yamazaki T, Miyatake S, Nozaki N, Kikuchi A, Saito T (Mar 1996). "Specific Interaction of Topoisomerase IIβ and the CD3ε Chain of the T Cell Receptor Complex". The Journal of Biological Chemistry. 271 (11): 6483–9. doi:10.1074/jbc.271.11.6483. PMID 8626450.

Further reading
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