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A subset of ATM‐ and ATR‐dependent phosphorylation events requires the BRCA1 protein
Author(s) -
Foray Nicolas,
Marot Didier,
Gabriel Anastasia,
Randrianarison Voahangy,
Carr Antony M.,
Perricaudet Michel,
Ashworth Alan,
Jeggo Penny
Publication year - 2003
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/cdg274
Subject(s) - carr , art history , library science , research centre , classics , operations research , art , history , computer science , biology , engineering , ecology
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 G 2 /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.