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BRCA1-A complex subunit RAP80

Definition:

Ubiquitin-binding protein. Specifically recognizes and binds 'Lys-63'-linked ubiquitin. Plays a central role in the BRCA1-A complex by specifically binding 'Lys-63'-linked ubiquitinated histones H2A and H2AX at DNA lesions sites, leading to target the BRCA1-BARD1 heterodimer to sites of DNA damage at double-strand breaks (DSBs). The BRCA1-A complex also possesses deubiquitinase activity that specifically removes 'Lys-63'-linked ubiquitin on histones H2A and H2AX. Also weakly binds monoubiquitin but with much less affinity than 'Lys-63'-linked ubiquitin. May interact with monoubiquitinated histones H2A and H2B; the relevance of such results is however unclear in vivo. Does not bind Lys-48'-linked ubiquitin. May indirectly act as a transcriptional repressor by inhibiting the interaction of NR6A1 with the corepressor NCOR1.

References:

[1]. Zixing Liu, et al. CCDC98 targets BRCA1 to DNA damage sites. Nat Struct Mol Biol. 2007 Aug;14(8):716-20. [Content Brief]

[2]. Lin Feng, et al. MERIT40 facilitates BRCA1 localization and DNA damage repair. Genes Dev. 2009 Mar 15;23(6):719-28. [Content Brief]

[3]. Jiaxue Wu, et al. Histone ubiquitination associates with BRCA1-dependent DNA damage response. Mol Cell Biol. 2009 Feb;29(3):849-60. [Content Brief]

[4]. Bijan Sobhian, et al. RAP80 targets BRCA1 to specific ubiquitin structures at DNA damage sites. Science. 2007 May 25;316(5828):1198-202. [Content Brief]

[5]. Hongtae Kim, et al. Ubiquitin-binding protein RAP80 mediates BRCA1-dependent DNA damage response. Science. 2007 May 25;316(5828):1202-5. [Content Brief]

[6]. Bin Wang, et al. Abraxas and RAP80 form a BRCA1 protein complex required for the DNA damage response. Science. 2007 May 25;316(5828):1194-8. [Content Brief]

[7]. Joshua J Sims, et al. Linkage-specific avidity defines the lysine 63-linked polyubiquitin-binding preference of rap80. Mol Cell. 2009 Mar 27;33(6):775-83. [Content Brief]

[8]. Anamika, et al. Molecular basis for impaired DNA damage response function associated with the RAP80 ΔE81 defect. J Biol Chem. 2014 May 2;289(18):12852-62. [Content Brief]

[9]. Zhijiang Yan, et al. RAP80, a novel nuclear protein that interacts with the retinoid-related testis-associated receptor. J Biol Chem. 2002 Aug 30;277(35):32379-88. [Content Brief]

[10]. Jun Yan, et al. The ubiquitin-interacting motif containing protein RAP80 interacts with BRCA1 and functions in DNA damage repair response. Cancer Res. 2007 Jul 15;67(14):6647-56. [Content Brief]

[11]. Genze Shao, et al. The Rap80-BRCC36 de-ubiquitinating enzyme complex antagonizes RNF8-Ubc13-dependent ubiquitination events at DNA double strand breaks. Proc Natl Acad Sci U S A. 2009 Mar 3;106(9):3166-71. [Content Brief]

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