| Structural highlights
Disease
ABRX1_HUMAN Disease susceptibility is associated with variants affecting the gene represented in this entry.
Function
ABRX1_HUMAN Involved in DNA damage response and double-strand break (DSB) repair. Component of the BRCA1-A complex, acting as a central scaffold protein that assembles the various components of the complex and mediates the recruitment of BRCA1. The BRCA1-A complex specifically recognizes 'Lys-63'-linked ubiquitinated histones H2A and H2AX at DNA lesion sites, leading to target the BRCA1-BARD1 heterodimer to sites of DNA damage at DSBs. This complex also possesses deubiquitinase activity that specifically removes 'Lys-63'-linked ubiquitin on histones H2A and H2AX.[1] [2] [3] [4] [5] [6] [7]
References
- ↑ Wang B, Matsuoka S, Ballif BA, Zhang D, Smogorzewska A, Gygi SP, Elledge SJ. Abraxas and RAP80 form a BRCA1 protein complex required for the DNA damage response. Science. 2007 May 25;316(5828):1194-8. PMID:17525340 doi:10.1126/science.1139476
- ↑ Liu Z, Wu J, Yu X. CCDC98 targets BRCA1 to DNA damage sites. Nat Struct Mol Biol. 2007 Aug;14(8):716-20. Epub 2007 Jul 22. PMID:17643121 doi:https://dx.doi.org/nsmb1279
- ↑ Kim H, Huang J, Chen J. CCDC98 is a BRCA1-BRCT domain-binding protein involved in the DNA damage response. Nat Struct Mol Biol. 2007 Aug;14(8):710-5. Epub 2007 Jul 22. PMID:17643122 doi:https://dx.doi.org/nsmb1277
- ↑ Wang B, Elledge SJ. Ubc13/Rnf8 ubiquitin ligases control foci formation of the Rap80/Abraxas/Brca1/Brcc36 complex in response to DNA damage. Proc Natl Acad Sci U S A. 2007 Dec 26;104(52):20759-63. Epub 2007 Dec 5. PMID:18077395 doi:https://dx.doi.org/0710061104
- ↑ Feng L, Huang J, Chen J. MERIT40 facilitates BRCA1 localization and DNA damage repair. Genes Dev. 2009 Mar 15;23(6):719-28. doi: 10.1101/gad.1770609. Epub 2009 Mar 4. PMID:19261748 doi:10.1101/gad.1770609
- ↑ Solyom S, Aressy B, Pylkäs K, Patterson-Fortin J, Hartikainen JM, Kallioniemi A, Kauppila S, Nikkilä J, Kosma VM, Mannermaa A, Greenberg RA, Winqvist R. Breast cancer-associated Abraxas mutation disrupts nuclear localization and DNA damage response functions. Sci Transl Med. 2012 Feb 22;4(122):122ra23. PMID:22357538 doi:10.1126/scitranslmed.3003223
- ↑ Wu Q, Paul A, Su D, Mehmood S, Foo TK, Ochi T, Bunting EL, Xia B, Robinson CV, Wang B, Blundell TL. Structure of BRCA1-BRCT/Abraxas Complex Reveals Phosphorylation-Dependent BRCT Dimerization at DNA Damage Sites. Mol Cell. 2016 Jan 13. pii: S1097-2765(15)00973-9. doi:, 10.1016/j.molcel.2015.12.017. PMID:26778126 doi:https://dx.doi.org/10.1016/j.molcel.2015.12.017
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