Functional interplay between BRCA2/FancD1 and FancC in DNA repair

Hiroyuki Kitao, Kazuhiko Yamamoto, Nobuko Matsushita, Mioko Ohzeki, Masamichi Ishiai, Minoru Takata

研究成果: Contribution to journalArticle査読

35 被引用数 (Scopus)

抄録

A rare hereditary disorder, Fanconi anemia (FA), is caused by mutations in an array of genes, which interact in a common FA pathway/network. These genes encode components of the FA "core" complex, a key factor FancD2, the familial breast cancer suppressor BRCA2/FancD1, and Brip1/FancJ helicase. Although BRCA2 is known to play a pivotal role in homologous recombination repair by regulating Rad51 recombinase, the precise functional relationship between BRCA2 and the other FA genes is unclear. Here we show that BRCA2-dependent chromatin loading of Rad51 after mitomycin C treatment was not compromised by disruption of FANCC or FANCD2. Rad51 and FancD2 form colocalizing subnuclear foci independently of each other. Furthermore, we created a conditional BRCA2 truncating mutation lacking the C-terminal conserved domain (CTD) (brca2ΔCTD), and disrupted the FANCC gene in this background. The fancc/ brca2ΔCTD double mutant revealed an epistatic relationship between FANCC and BRCA2 CTD in terms of x-ray sensitivity. In contrast, levels of cisplatin sensitivity and mitomycin C-induced chromosomal aberrations were increased in fancc/brca2ΔCTD cells relative to either single mutant. Taken together, these results indicate that FA proteins work together with BRCA2/Rad51-mediated homologous recombination in double strand break repair, whereas the FA pathway plays a role that is independent of the CTD of BRCA2 in interstrand cross-link repair. These results provide insights in to the functional interplay between the classical FA pathway and BRCA2.

本文言語英語
ページ(範囲)21312-21320
ページ数9
ジャーナルJournal of Biological Chemistry
281
30
DOI
出版ステータス出版済み - 7 28 2006
外部発表はい

All Science Journal Classification (ASJC) codes

  • 生化学
  • 分子生物学
  • 細胞生物学

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