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

Research output: Contribution to journalArticle

112 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)34-43
Number of pages10
JournalMolecular and cellular biology
Volume25
Issue number1
DOIs
Publication statusPublished - Jan 1 2005

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Fanconi Anemia Complementation Group Proteins
Gene Conversion
Immunoglobulin Genes
Homologous Recombination
DNA Repair
DNA Damage
Immunoglobulin Light Chains
L Forms
Recombinational DNA Repair
Multiprotein Complexes
Sister Chromatid Exchange
Double-Stranded DNA Breaks
Protein C
Chickens
B-Lymphocytes
Cell Line
Mutation

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

Cite this

Fanconi anemia protein FANCD2 promotes immunoglobulin gene conversion and DNA repair through a mechanism related to homologous recombination. / Yamamoto, Kazuhiko; Hirano, Seiki; Ishiai, Masamichi; Morishima, Kenichi; Kitao, Hiroyuki; Namikoshi, Keiko; Kimura, Masayo; Matsushita, Nobuko; Arakawa, Hiroshi; Buerstedde, Jean Marie; Komatsu, Kenshi; Thompson, Larry H.; Takata, Minoru.

In: Molecular and cellular biology, Vol. 25, No. 1, 01.01.2005, p. 34-43.

Research output: Contribution to journalArticle

Yamamoto, K, Hirano, S, Ishiai, M, Morishima, K, Kitao, H, Namikoshi, K, Kimura, M, Matsushita, N, Arakawa, H, Buerstedde, JM, Komatsu, K, Thompson, LH & Takata, M 2005, 'Fanconi anemia protein FANCD2 promotes immunoglobulin gene conversion and DNA repair through a mechanism related to homologous recombination', Molecular and cellular biology, vol. 25, no. 1, pp. 34-43. https://doi.org/10.1128/MCB.25.1.34-43.2005
Yamamoto, Kazuhiko ; Hirano, Seiki ; Ishiai, Masamichi ; Morishima, Kenichi ; Kitao, Hiroyuki ; Namikoshi, Keiko ; Kimura, Masayo ; Matsushita, Nobuko ; Arakawa, Hiroshi ; Buerstedde, Jean Marie ; Komatsu, Kenshi ; Thompson, Larry H. ; Takata, Minoru. / Fanconi anemia protein FANCD2 promotes immunoglobulin gene conversion and DNA repair through a mechanism related to homologous recombination. In: Molecular and cellular biology. 2005 ; Vol. 25, No. 1. pp. 34-43.
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