TOP2B

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

TOP2B
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 3QX3, 4G0U, 4G0V, 4G0W, 4J3N
Identifiers
Aliases	TOP2B, TOPIIB, top2beta, topoisomerase (DNA) II beta, DNA topoisomerase II beta
External IDs	OMIM: 126431 MGI: 98791 HomoloGene: 134711 GeneCards: TOP2B
Gene location (Human) Chr. Chromosome 3 (human)[1] Band 3p24.2 Start 25,597,905 bp[1] End 25,664,907 bp[1]
Gene location (Mouse) Chr. Chromosome 14 (mouse)[2] Band 14|14 A2 Start 16,365,179 bp[2] End 16,435,462 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • GO:0003918 DNA topoisomerase type II (double strand cut, ATP-hydrolyzing) activity • nucleotide binding • DNA binding • histone deacetylase binding • chromatin binding • isomerase activity • metal ion binding • DNA topoisomerase activity • protein C-terminus binding • protein heterodimerization activity • enzyme binding • ATP binding • protein kinase C binding • ribonucleoprotein complex binding Cellular component • cytosol • nucleoplasm • heterochromatin • nucleolus • cell nucleus • cytoplasm • ribonucleoprotein • viral integration complex Biological process • resolution of meiotic recombination intermediates • axonogenesis • DNA metabolic process • neuron migration • forebrain development • mitotic DNA integrity checkpoint • sister chromatid segregation • DNA topological change • positive regulation of single stranded viral RNA replication via double stranded DNA intermediate Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
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 Mb	Chr 14: 16.37 – 16.44 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/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:

• BAZ1B,[10]
• HDAC1,[11][12]
• Histone deacetylase 2,[11]
• P53,[13]
• Small ubiquitin-related modifier 1[14] and
• T-cell surface glycoprotein CD3 epsilon chain.[15]

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

• Champoux JJ (2002). "DNA topoisomerases: structure, function, and mechanism". Annual Review of Biochemistry. 70: 369–413. doi:10.1146/annurev.biochem.70.1.369. PMID 11395412.
• Austin CA, Fisher LM (Jun 1990). "Isolation and characterization of a human cDNA clone encoding a novel DNA topoisomerase II homologue from HeLa cells". FEBS Letters. 266 (1–2): 115–7. doi:10.1016/0014-5793(90)81520-X. PMID 2163884. S2CID 46581515.
• Chung TD, Drake FH, Tan KB, Per SR, Crooke ST, Mirabelli CK (Dec 1989). "Characterization and immunological identification of cDNA clones encoding two human DNA topoisomerase II isozymes". Proceedings of the National Academy of Sciences of the United States of America. 86 (23): 9431–5. Bibcode:1989PNAS...86.9431C. doi:10.1073/pnas.86.23.9431. PMC 298510. PMID 2556712.
• Austin CA, Sng JH, Patel S, Fisher LM (Mar 1993). "Novel HeLa topoisomerase II is the II beta isoform: complete coding sequence and homology with other type II topoisomerases". Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression. 1172 (3): 283–91. doi:10.1016/0167-4781(93)90215-Y. PMID 8383537.
• Davies SL, Jenkins JR, Hickson ID (Aug 1993). "Human cells express two differentially spliced forms of topoisomerase II beta mRNA". Nucleic Acids Research. 21 (16): 3719–23. doi:10.1093/nar/21.16.3719. PMC 309874. PMID 8396237.
• 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.
• Biersack H, Jensen S, Gromova I, Nielsen IS, Westergaard O, Andersen AH (Aug 1996). "Active heterodimers are formed from human DNA topoisomerase II alpha and II beta isoforms". Proceedings of the National Academy of Sciences of the United States of America. 93 (16): 8288–93. doi:10.1073/pnas.93.16.8288. PMC 38663. PMID 8710863.
• Meyer KN, Kjeldsen E, Straub T, Knudsen BR, Hickson ID, Kikuchi A, Kreipe H, Boege F (Feb 1997). "Cell cycle-coupled relocation of types I and II topoisomerases and modulation of catalytic enzyme activities". The Journal of Cell Biology. 136 (4): 775–88. doi:10.1083/jcb.136.4.775. PMC 2132491. PMID 9049244.
• Fukunaga R, Hunter T (Apr 1997). "MNK1, a new MAP kinase-activated protein kinase, isolated by a novel expression screening method for identifying protein kinase substrates". The EMBO Journal. 16 (8): 1921–33. doi:10.1093/emboj/16.8.1921. PMC 1169795. PMID 9155018.
• Ng SW, Liu Y, Schnipper LE (Dec 1997). "Cloning and characterization of the 5′-flanking sequence for the human DNA topoisomerase II beta gene". Gene. 203 (2): 113–9. doi:10.1016/S0378-1119(97)00500-3. PMID 9426241.
• Yamane K, Kawabata M, Tsuruo T (Dec 1997). "A DNA-topoisomerase-II-binding protein with eight repeating regions similar to DNA-repair enzymes and to a cell-cycle regulator". European Journal of Biochemistry / FEBS. 250 (3): 794–9. doi:10.1111/j.1432-1033.1997.00794.x. PMID 9461304.
• Cowell IG, Willmore E, Chalton D, Marsh KL, Jazrawi E, Fisher LM, Austin CA (Sep 1998). "Nuclear distribution of human DNA topoisomerase IIbeta: a nuclear targeting signal resides in the 116-residue C-terminal tail". Experimental Cell Research. 243 (2): 232–40. doi:10.1006/excr.1998.4150. PMID 9743583.
• Lang AJ, Mirski SE, Cummings HJ, Yu Q, Gerlach JH, Cole SP (Oct 1998). "Structural organization of the human TOP2A and TOP2B genes". Gene. 221 (2): 255–66. doi:10.1016/S0378-1119(98)00468-5. PMID 9795238.
• Sng JH, Heaton VJ, Bell M, Maini P, Austin CA, Fisher LM (Mar 1999). "Molecular cloning and characterization of the human topoisomerase IIα and IIβ genes: Evidence for isoform evolution through gene duplication". Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression. 1444 (3): 395–406. doi:10.1016/S0167-4781(99)00020-2. PMID 10095062.
• Bjergbaek L, Jensen S, Westergaard O, Andersen AH (Sep 1999). "Using a Biochemical Approach to Identify the Primary Dimerization Regions in Human DNA Topoisomerase IIα". The Journal of Biological Chemistry. 274 (37): 26529–36. doi:10.1074/jbc.274.37.26529. PMID 10473615.
• 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.
• 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.
• Mirski SE, Voskoglou-Nomikos T, Young LC, Deeley RG, Campling BG, Gerlach JH, Cole SP (Jun 2000). "Simultaneous Quantitation of Topoisomerase II α and β Isoform mRNAs in Lung Tumor Cells and Normal and Malignant Lung Tissue". Laboratory Investigation. 80 (6): 787–95. doi:10.1038/labinvest.3780083. PMID 10879730.