TOPBP1

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External IDs	GeneCards: [1]
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	Wikidata
View/Edit Human

DNA topoisomerase 2-binding protein 1 is an enzyme that in humans is encoded by the TOPBP1 gene.^[1]^[2]^[3]

Function

This gene encodes a binding protein which interacts with the C-terminal region of topoisomerase II beta. This interaction suggests a supportive role for this protein in the catalytic reactions of topoisomerase II beta through transient breakages of DNA strands.^[3]

Meiotic silencing

In mammals, surveillance mechanisms remove meiotic cells in which chromosome synapsis is defective. One such surveillance mechanism is meiotic silencing, the transcriptional silencing of genes on asynapsed chromosomes.^[4] TOPBP1, a DNA damage response protein, has a crucial role in meiotic sex chromosome silencing.^[4]

Interactions

TOPBP1 has been shown to interact with:

Clinical relevance

This gene may be involved in the development of ovarian and breast cancer.^[11]

Mutations in TOPBP1 cause Idiopathic pulmonary arterial hypertension .^[12]

References

↑ 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.
↑ Nagase T, Seki N, Ishikawa K, Ohira M, Kawarabayasi Y, Ohara O, Tanaka A, Kotani H, Miyajima N, Nomura N (Oct 1996). "Prediction of the coding sequences of unidentified human genes. VI. The coding sequences of 80 new genes (KIAA0201-KIAA0280) deduced by analysis of cDNA clones from cell line KG-1 and brain". DNA Research. 3 (5): 321–9, 341–54. doi:10.1093/dnares/3.5.321. PMID 9039502.
↑ ^3.0 ^3.1 "Entrez Gene: TOPBP1 topoisomerase (DNA) II binding protein 1".
↑ ^4.0 ^4.1 ElInati E, Russell HR, Ojarikre OA, Sangrithi M, Hirota T, de Rooij DG, McKinnon PJ, Turner JM (2017). "DNA damage response protein TOPBP1 regulates X chromosome silencing in the mammalian germ line". Proc. Natl. Acad. Sci. U.S.A. 114 (47): 12536–12541. doi:10.1073/pnas.1712530114. PMC 5703310. PMID 29114052.
↑ Liu K, Lin FT, Ruppert JM, Lin WC (May 2003). "Regulation of E2F1 by BRCT domain-containing protein TopBP1". Molecular and Cellular Biology. 23 (9): 3287–304. doi:10.1128/mcb.23.9.3287-3304.2003. PMC 153207. PMID 12697828.
↑ Yu X, Chini CC, He M, Mer G, Chen J (Oct 2003). "The BRCT domain is a phospho-protein binding domain". Science. 302 (5645): 639–42. doi:10.1126/science.1088753. PMID 14576433.
↑ Xu ZX, Timanova-Atanasova A, Zhao RX, Chang KS (Jun 2003). "PML colocalizes with and stabilizes the DNA damage response protein TopBP1". Molecular and Cellular Biology. 23 (12): 4247–56. doi:10.1128/mcb.23.12.4247-4256.2003. PMC 156140. PMID 12773567.
↑ Mäkiniemi M, Hillukkala T, Tuusa J, Reini K, Vaara M, Huang D, Pospiech H, Majuri I, Westerling T, Mäkelä TP, Syväoja JE (Aug 2001). "BRCT domain-containing protein TopBP1 functions in DNA replication and damage response". The Journal of Biological Chemistry. 276 (32): 30399–406. doi:10.1074/jbc.M102245200. PMID 11395493.
↑ Honda Y, Tojo M, Matsuzaki K, Anan T, Matsumoto M, Ando M, Saya H, Nakao M (Feb 2002). "Cooperation of HECT-domain ubiquitin ligase hHYD and DNA topoisomerase II-binding protein for DNA damage response". The Journal of Biological Chemistry. 277 (5): 3599–605. doi:10.1074/jbc.M104347200. PMID 11714696.
↑ Herold S, Wanzel M, Beuger V, Frohme C, Beul D, Hillukkala T, Syvaoja J, Saluz HP, Haenel F, Eilers M (Sep 2002). "Negative regulation of the mammalian UV response by Myc through association with Miz-1". Molecular Cell. 10 (3): 509–21. doi:10.1016/s1097-2765(02)00633-0. PMID 12408820.
↑ Forma E, Wójcik-Krowiranda K, Bieńkiewicz A, Bryś M (2013) Molecular basis of gynecological oncology - TopBP1 protein as the guardian of genome integrity. Ginekol Pol 84(5):373-376
↑ de Jesus Perez VA, Yuan K, Lyuksyutova MA, Dewey F, Orcholski ME, Shuffle EM, Mathur M, Yancy L, Rojas V, Li CG, Cao A, Alastalo TP, Khazeni N, Cimprich KA, Butte AJ, Ashley E, Zamanian RT (May 2014). "Whole-exome sequencing reveals TopBP1 as a novel gene in idiopathic pulmonary arterial hypertension". American Journal of Respiratory and Critical Care Medicine. 189 (10): 1260–72. doi:10.1164/rccm.201310-1749OC. PMC 4225850. PMID 24702692.

Yamane K, Tsuruo T (Sep 1999). "Conserved BRCT regions of TopBP1 and of the tumor suppressor BRCA1 bind strand breaks and termini of DNA". Oncogene. 18 (37): 5194–203. doi:10.1038/sj.onc.1202922. PMID 10498869.
Mäkiniemi M, Hillukkala T, Tuusa J, Reini K, Vaara M, Huang D, Pospiech H, Majuri I, Westerling T, Mäkelä TP, Syväoja JE (Aug 2001). "BRCT domain-containing protein TopBP1 functions in DNA replication and damage response". The Journal of Biological Chemistry. 276 (32): 30399–406. doi:10.1074/jbc.M102245200. PMID 11395493.
Honda Y, Tojo M, Matsuzaki K, Anan T, Matsumoto M, Ando M, Saya H, Nakao M (Feb 2002). "Cooperation of HECT-domain ubiquitin ligase hHYD and DNA topoisomerase II-binding protein for DNA damage response". The Journal of Biological Chemistry. 277 (5): 3599–605. doi:10.1074/jbc.M104347200. PMID 11714696.
Yamane K, Wu X, Chen J (Jan 2002). "A DNA damage-regulated BRCT-containing protein, TopBP1, is required for cell survival". Molecular and Cellular Biology. 22 (2): 555–66. doi:10.1128/MCB.22.2.555-566.2002. PMC 139754. PMID 11756551.
Boner W, Taylor ER, Tsirimonaki E, Yamane K, Campo MS, Morgan IM (Jun 2002). "A Functional interaction between the human papillomavirus 16 transcription/replication factor E2 and the DNA damage response protein TopBP1". The Journal of Biological Chemistry. 277 (25): 22297–303. doi:10.1074/jbc.M202163200. PMID 11934899.
Herold S, Wanzel M, Beuger V, Frohme C, Beul D, Hillukkala T, Syvaoja J, Saluz HP, Haenel F, Eilers M (Sep 2002). "Negative regulation of the mammalian UV response by Myc through association with Miz-1". Molecular Cell. 10 (3): 509–21. doi:10.1016/S1097-2765(02)00633-0. PMID 12408820.
Nakayama M, Kikuno R, Ohara O (Nov 2002). "Protein-protein interactions between large proteins: two-hybrid screening using a functionally classified library composed of long cDNAs". Genome Research. 12 (11): 1773–84. doi:10.1101/gr.406902. PMC 187542. PMID 12421765.
Liu K, Lin FT, Ruppert JM, Lin WC (May 2003). "Regulation of E2F1 by BRCT domain-containing protein TopBP1". Molecular and Cellular Biology. 23 (9): 3287–304. doi:10.1128/MCB.23.9.3287-3304.2003. PMC 153207. PMID 12697828.
Xu ZX, Timanova-Atanasova A, Zhao RX, Chang KS (Jun 2003). "PML colocalizes with and stabilizes the DNA damage response protein TopBP1". Molecular and Cellular Biology. 23 (12): 4247–56. doi:10.1128/MCB.23.12.4247-4256.2003. PMC 156140. PMID 12773567.
Yamane K, Chen J, Kinsella TJ (Jun 2003). "Both DNA topoisomerase II-binding protein 1 and BRCA1 regulate the G2-M cell cycle checkpoint". Cancer Research. 63 (12): 3049–53. PMID 12810625.
Greer DA, Besley BD, Kennedy KB, Davey S (Aug 2003). "hRad9 rapidly binds DNA containing double-strand breaks and is required for damage-dependent topoisomerase II beta binding protein 1 focus formation". Cancer Research. 63 (16): 4829–35. PMID 12941802.
Manke IA, Lowery DM, Nguyen A, Yaffe MB (Oct 2003). "BRCT repeats as phosphopeptide-binding modules involved in protein targeting". Science. 302 (5645): 636–9. doi:10.1126/science.1088877. PMID 14576432.
Yu X, Chini CC, He M, Mer G, Chen J (Oct 2003). "The BRCT domain is a phospho-protein binding domain". Science. 302 (5645): 639–42. doi:10.1126/science.1088753. PMID 14576433.
Liu K, Luo Y, Lin FT, Lin WC (Mar 2004). "TopBP1 recruits Brg1/Brm to repress E2F1-induced apoptosis, a novel pRb-independent and E2F1-specific control for cell survival". Genes & Development. 18 (6): 673–86. doi:10.1101/gad.1180204. PMC 387242. PMID 15075294.
Reini K, Uitto L, Perera D, Moens PB, Freire R, Syväoja JE (May 2004). "TopBP1 localises to centrosomes in mitosis and to chromosome cores in meiosis". Chromosoma. 112 (7): 323–30. doi:10.1007/s00412-004-0277-5. PMID 15138768.
Hassel S, Eichner A, Yakymovych M, Hellman U, Knaus P, Souchelnytskyi S (May 2004). "Proteins associated with type II bone morphogenetic protein receptor (BMPR-II) and identified by two-dimensional gel electrophoresis and mass spectrometry". Proteomics. 4 (5): 1346–58. doi:10.1002/pmic.200300770. PMID 15188402.
Yoshida K, Inoue I (Aug 2004). "Expression of MCM10 and TopBP1 is regulated by cell proliferation and UV irradiation via the E2F transcription factor". Oncogene. 23 (37): 6250–60. doi:10.1038/sj.onc.1207829. PMID 15195143.

[pmid9461304-1] 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.

[pmid9039502-2] Nagase T, Seki N, Ishikawa K, Ohira M, Kawarabayasi Y, Ohara O, Tanaka A, Kotani H, Miyajima N, Nomura N (Oct 1996). "Prediction of the coding sequences of unidentified human genes. VI. The coding sequences of 80 new genes (KIAA0201-KIAA0280) deduced by analysis of cDNA clones from cell line KG-1 and brain". DNA Research. 3 (5): 321–9, 341–54. doi:10.1093/dnares/3.5.321. PMID 9039502.

[entrez-3] 3.0 ^3.1 "Entrez Gene: TOPBP1 topoisomerase (DNA) II binding protein 1".

[pmid29114052-4] 4.0 ^4.1 ElInati E, Russell HR, Ojarikre OA, Sangrithi M, Hirota T, de Rooij DG, McKinnon PJ, Turner JM (2017). "DNA damage response protein TOPBP1 regulates X chromosome silencing in the mammalian germ line". Proc. Natl. Acad. Sci. U.S.A. 114 (47): 12536–12541. doi:10.1073/pnas.1712530114. PMC 5703310. PMID 29114052.

[pmid12697828-5] Liu K, Lin FT, Ruppert JM, Lin WC (May 2003). "Regulation of E2F1 by BRCT domain-containing protein TopBP1". Molecular and Cellular Biology. 23 (9): 3287–304. doi:10.1128/mcb.23.9.3287-3304.2003. PMC 153207. PMID 12697828.

[pmid14576433-6] Yu X, Chini CC, He M, Mer G, Chen J (Oct 2003). "The BRCT domain is a phospho-protein binding domain". Science. 302 (5645): 639–42. doi:10.1126/science.1088753. PMID 14576433.

[pmid12773567-7] Xu ZX, Timanova-Atanasova A, Zhao RX, Chang KS (Jun 2003). "PML colocalizes with and stabilizes the DNA damage response protein TopBP1". Molecular and Cellular Biology. 23 (12): 4247–56. doi:10.1128/mcb.23.12.4247-4256.2003. PMC 156140. PMID 12773567.

[pmid11395493-8] Mäkiniemi M, Hillukkala T, Tuusa J, Reini K, Vaara M, Huang D, Pospiech H, Majuri I, Westerling T, Mäkelä TP, Syväoja JE (Aug 2001). "BRCT domain-containing protein TopBP1 functions in DNA replication and damage response". The Journal of Biological Chemistry. 276 (32): 30399–406. doi:10.1074/jbc.M102245200. PMID 11395493.

[pmid11714696-9] Honda Y, Tojo M, Matsuzaki K, Anan T, Matsumoto M, Ando M, Saya H, Nakao M (Feb 2002). "Cooperation of HECT-domain ubiquitin ligase hHYD and DNA topoisomerase II-binding protein for DNA damage response". The Journal of Biological Chemistry. 277 (5): 3599–605. doi:10.1074/jbc.M104347200. PMID 11714696.

[pmid12408820-10] Herold S, Wanzel M, Beuger V, Frohme C, Beul D, Hillukkala T, Syvaoja J, Saluz HP, Haenel F, Eilers M (Sep 2002). "Negative regulation of the mammalian UV response by Myc through association with Miz-1". Molecular Cell. 10 (3): 509–21. doi:10.1016/s1097-2765(02)00633-0. PMID 12408820.

[Forma2013-11] Forma E, Wójcik-Krowiranda K, Bieńkiewicz A, Bryś M (2013) Molecular basis of gynecological oncology - TopBP1 protein as the guardian of genome integrity. Ginekol Pol 84(5):373-376

[12] Jesus Perez VA, Yuan K, Lyuksyutova MA, Dewey F, Orcholski ME, Shuffle EM, Mathur M, Yancy L, Rojas V, Li CG, Cao A, Alastalo TP, Khazeni N, Cimprich KA, Butte AJ, Ashley E, Zamanian RT (May 2014). "Whole-exome sequencing reveals TopBP1 as a novel gene in idiopathic pulmonary arterial hypertension". American Journal of Respiratory and Critical Care Medicine. 189 (10): 1260–72. doi:10.1164/rccm.201310-1749OC. PMC 4225850. PMID 24702692.

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TOPBP1

Contents

Function

Meiotic silencing

Interactions

Clinical relevance

References

Further reading

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