Reactome | Formation of BRCA1-A complex at DNA DSBs

Formation of BRCA1-A complex at DNA DSBs

Stable Identifier

R-HSA-5683385

Type

Reaction [binding]

Species

Homo sapiens

Compartment

nucleoplasm

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Formation of BRCA1-A complex at DNA DSBs

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A DNA damage-independent phosphorylation of FAM175A (Abraxas) serine residue S406 creates a pS-X-X-F (phospho-Ser-X-X-Phe) motif that binds BRCT repeats of BRCA1. The BRCA1 cancer predisposing mutation M1775R (Met1775Arg) inhibits BRCA1 binding to FAM175A. FAM175A interaction with UIMC1 (RAP80) enables BRCA1 recruitment to DNA double strand breaks (DSBs) (Wang et al. 2007). In addition to BRCA1, FAM175A also interacts with BRCC3 (BRCC36) (Wang et al. 2007, Hu et al. 2011) and BABAM1 (MERIT40, NBA1) (Vikrant et al. 2014). BABAM1 simultaneously interacts with BRE (BRCC45) (Hu et al. 2011). Together, BRCA1, BARD1, UIMC1, FAM175A, BRCC36, BRE and BABAM1 form the so-called BRCA1-A complex at DNA DSBs (Wang et al. 2009).

Literature References

PubMed ID	Title	Journal	Year
24667604	Role of MERIT40 in stabilization of BRCA1 complex: a protein-protein interaction study Vikrant, -, Sawant, UU, Varma, AK	Biochem. Biophys. Res. Commun.	2014
21282113	NBA1/MERIT40 and BRE interaction is required for the integrity of two distinct deubiquitinating enzyme BRCC36-containing complexes Hu, X, Kim, JA, Castillo, A, Huang, M, Liu, J, Wang, B	J. Biol. Chem.	2011
19261749	NBA1, a new player in the Brca1 A complex, is required for DNA damage resistance and checkpoint control Wang, B, Hurov, K, Hofmann, K, Elledge, SJ	Genes Dev.	2009
17525340	Abraxas and RAP80 form a BRCA1 protein complex required for the DNA damage response Wang, B, Matsuoka, S, Ballif, BA, Zhang, D, Smogorzewska, A, Gygi, SP, Elledge, SJ	Science	2007