A subset of ATM- and ATR-dependent phosphorylation events requires the BRCA1 protein

Foray, Nicolas, Marot, Didier, Gabriel, Anastasia, Randrianarison, Voahangy, Carr, Antony M, Perricaudet, Michel, Ashworth, Alan and Jeggo, Penny (2003) A subset of ATM- and ATR-dependent phosphorylation events requires the BRCA1 protein. EMBO Journal, 22 (11). pp. 2860-2871. ISSN 0261-4189

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BRCA1 is a central component of the DNA damage response mechanism and defects in BRCA1 confer sensitivity to a broad range of DNA damaging agents. BRCA1 is required for homologous recombination and DNA damage-induced S and G2/M phase arrest. We show here that BRCA1 is required for ATM- and ATR-dependent phosphorylation of p53, c-Jun, Nbs1 and Chk2 following exposure to ionizing or ultraviolet radiation, respectively, and is also required for ATM phosphorylation of CtIP. In contrast, DNA damage-induced phosphorylation of the histone variant H2AX is independent of BRCA1. We also show that the presence of BRCA1 is dispensable for DNA damage-induced phosphorylation of Rad9, Hus1 and Rad17, and for the relocalization of Rad9 and Hus1. We propose that BRCA1 facilitates the ability of ATM and ATR to phosphorylate downstream substrates that directly influence cell cycle checkpoint arrest and apoptosis, but that BRCA1 is dispensable for the phosphorylation of DNA-associated ATM and ATR substrates.

Item Type: Article
Schools and Departments: School of Life Sciences > Sussex Centre for Genome Damage and Stability
Depositing User: Antony Carr
Date Deposited: 06 Feb 2012 18:43
Last Modified: 14 Jun 2012 08:10
URI: http://sro.sussex.ac.uk/id/eprint/17965
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