CtIP- and ATR-dependent FANCJ phosphorylation in response to DNA strand breaks mediated by DNA replication

Ryo Sakasai, Akiko Sakai, Makoto Iimori, Shinichi Kiyonari, Kazuaki Matsuoka, Yoshihiro Kakeji, Hiroyuki Kitao, Yoshihiko Maehara

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

FANCJ, also called BACH1/BRIP1, is a 5′-3′ DEAH helicase, whose mutations are known as a risk factor for Fanconi 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 BRCA1 and TopBP1, 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 TopBP1 and ATM-Rad3 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-TopBP1 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-TopBP1 complex formation in response to replication-coupled DSBs.

Original languageEnglish
Pages (from-to)962-970
Number of pages9
JournalGenes to Cells
Volume17
Issue number12
DOIs
Publication statusPublished - Dec 1 2012

Fingerprint

Camptothecin
DNA Breaks
Double-Stranded DNA Breaks
DNA Replication
S Phase Cell Cycle Checkpoints
Phosphorylation
Fanconi Anemia
Sexual Partners
DNA
Ovarian Neoplasms
DNA Damage
Phosphotransferases
Breast Neoplasms
Mutation
Proteins
Therapeutics
1,2-di-(4-sulfamidophenyl)-4-butylpyrazolidine-3,5-dione

All Science Journal Classification (ASJC) codes

  • Genetics
  • Cell Biology

Cite this

CtIP- and ATR-dependent FANCJ phosphorylation in response to DNA strand breaks mediated by DNA replication. / Sakasai, Ryo; Sakai, Akiko; Iimori, Makoto; Kiyonari, Shinichi; Matsuoka, Kazuaki; Kakeji, Yoshihiro; Kitao, Hiroyuki; Maehara, Yoshihiko.

In: Genes to Cells, Vol. 17, No. 12, 01.12.2012, p. 962-970.

Research output: Contribution to journalArticle

Sakasai, Ryo ; Sakai, Akiko ; Iimori, Makoto ; Kiyonari, Shinichi ; Matsuoka, Kazuaki ; Kakeji, Yoshihiro ; Kitao, Hiroyuki ; Maehara, Yoshihiko. / CtIP- and ATR-dependent FANCJ phosphorylation in response to DNA strand breaks mediated by DNA replication. In: Genes to Cells. 2012 ; Vol. 17, No. 12. pp. 962-970.
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