Fanconi anemia protein FANCD2 promotes immunoglobulin gene conversion and DNA repair through a mechanism related to homologous recombination

Kazuhiko Yamamoto, Seiki Hirano, Masamichi Ishiai, Kenichi Morishima, Hiroyuki Kitao, Keiko Namikoshi, Masayo Kimura, Nobuko Matsushita, Hiroshi Arakawa, Jean Marie Buerstedde, Kenshi Komatsu, Larry H. Thompson, Minoru Takata

研究成果: Contribution to journalArticle査読

115 被引用数 (Scopus)

抄録

Recent studies show overlap between Fanconi anemia (FA) proteins and those involved in DNA repair mediated by homologous recombination (HR). However, the mechanism by which FA proteins affect HR is unclear. FA proteins (FancA/C/E/F/G/L) form a multiprotein complex, which is responsible for DNA damage-induced FancD2 monoubiquitination, a key event for cellular resistance to DNA damage. Here, we show that FANCD2-disrupted DT40 chicken B-cell line is defective in HR-mediated DNA double-strand break (DSB) repair, as well as gene conversion at the immunoglobulin light-chain locus, an event also mediated by HR. Gene conversions occurring in mutant cells were associated with decreased nontemplated mutations. In contrast to these defects, we also found increased spontaneous sister chromatid exchange (SCE) and intact Rad51 foci formation after DNA damage. Thus, we propose that FancD2 promotes a subpathway of HR that normally mediates gene conversion by a mechanism that avoids crossing over and hence SCEs.

本文言語英語
ページ(範囲)34-43
ページ数10
ジャーナルMolecular and cellular biology
25
1
DOI
出版ステータス出版済み - 1 2005
外部発表はい

All Science Journal Classification (ASJC) codes

  • 分子生物学
  • 細胞生物学

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