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C t IP ‐ and ATR ‐dependent FANCJ phosphorylation in response to DNA strand breaks mediated by DNA replication
Author(s) -
Sakasai Ryo,
Sakai Akiko,
Iimori Makoto,
Kiyonari Shinichi,
Matsuoka Kazuaki,
Kakeji Yoshihiro,
Kitao Hiroyuki,
Maehara Yoshihiko
Publication year - 2012
Publication title -
genes to cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.912
H-Index - 115
eISSN - 1365-2443
pISSN - 1356-9597
DOI - 10.1111/gtc.12011
Subject(s) - hyperphosphorylation , biology , dna damage , dna replication , fanconi anemia , phosphorylation , microbiology and biotechnology , helicase , dna repair , dna , genetics , gene , rna
FANCJ , also called BACH 1/ BRIP 1, is a 5′‐3′ DEAH helicase, whose mutations are known as a risk factor for F anconi anemia and also breast and ovarian cancer. FANCJ is thought to contribute to DNA double‐strand break ( DSB ) repair and S ‐phase checkpoint through binding to multiple partner proteins, such as BRCA 1 and T op BP 1, but its molecular regulation remains unclear. We focused on DNA damage‐induced phosphorylation of FANCJ and found that reagents that cause DSB or replication fork stalling induce FANCJ hyperphosphorylation. In particular, camptothecin ( CPT ) induced rapid and efficient FANCJ hyperphosphorylation that was largely dependent on T op BP 1 and ATM ‐ R ad3 related ( ATR ) kinase. Furthermore, DNA end resection that exposes single‐strand DNA at the DSB site was required for hyperphosphorylation. Interestingly, upon CPT treatment, a dramatic increase in the FANCJ – T op BP 1 complex was observed, and this increase was not alleviated even when ATR ‐dependent hyperphosphorylation was suppressed. These results suggest that FANCJ function may be modulated by hyperphosphorylation in a DNA end resection‐ and ATR ‐dependent manner and by FANCJ –Top BP 1 complex formation in response to replication‐coupled DSB s.