Reactome | BRCA1 binds phosphorylated RBBP8

BRCA1 binds phosphorylated RBBP8

Stable Identifier

R-HSA-5684108

Type

Reaction [binding]

Species

Homo sapiens

Compartment

nucleoplasm

ReviewStatus

5/5

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BRCA1:BARD1 complex binds RBBP8 (CtIP) phosphorylated by CDK2 at DNA double-strand breaks (DSBs), thus forming the so-called BRCA1-C complex. As active CDK2 in complex with CCNA (cyclin A) exists only in the S and G2 phases of the cell cycle, this limits the formation of BRCA1 complex with RBBP8 and the consequent initiation of homologous recombination to S and G2 phases, when the genome is duplicated and sister chromatids are available (Chen et al. 2008, Yun and Hiom 2009). Dissociation of the BRCA1-A complex is necessary for BRCA1 to be able to bind RBBP8 (Coleman and Greenberg 2011). Phosphorylation of BRCA1 by CHEK2 also contributes to the initiation of homologous recombination, with this phosphorylation similarly serving as a molecular clock (Parameswaran et al. 2015).

Literature References

PubMed ID	Title	Journal	Year
21335604	The BRCA1-RAP80 complex regulates DNA repair mechanism utilization by restricting end resection Coleman, KA, Greenberg, RA	J. Biol. Chem.	2011
18171670	Cell cycle-dependent complex formation of BRCA1.CtIP.MRN is important for DNA double-strand break repair Chen, L, Nievera, CJ, Lee, AY, Wu, X	J. Biol. Chem.	2008
25659039	Damage-induced BRCA1 phosphorylation by Chk2 contributes to the timing of end resection Parameswaran, B, Chiang, HC, Lu, Y, Coates, J, Deng, CX, Baer, RJ, Lin, HK, Li, R, Paull, TT, Hu, Y	Cell Cycle	2015
19357644	CtIP-BRCA1 modulates the choice of DNA double-strand-break repair pathway throughout the cell cycle Yun, MH, Hiom, K	Nature	2009