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 language | English |
|---|---|
| Pages (from-to) | 34-43 |
| Number of pages | 10 |
| Journal | Molecular and cellular biology |
| Volume | 25 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - Jan 1 2005 |
| Externally published | Yes |
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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 journal › Article
}
TY - JOUR
T1 - Fanconi anemia protein FANCD2 promotes immunoglobulin gene conversion and DNA repair through a mechanism related to homologous recombination
AU - Yamamoto, Kazuhiko
AU - Hirano, Seiki
AU - Ishiai, Masamichi
AU - Morishima, Kenichi
AU - Kitao, Hiroyuki
AU - Namikoshi, Keiko
AU - Kimura, Masayo
AU - Matsushita, Nobuko
AU - Arakawa, Hiroshi
AU - Buerstedde, Jean Marie
AU - Komatsu, Kenshi
AU - Thompson, Larry H.
AU - Takata, Minoru
PY - 2005/1/1
Y1 - 2005/1/1
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=19944411110&partnerID=8YFLogxK
U2 - 10.1128/MCB.25.1.34-43.2005
DO - 10.1128/MCB.25.1.34-43.2005
M3 - Article
C2 - 15601828
AN - SCOPUS:19944411110
VL - 25
SP - 34
EP - 43
JO - Molecular and Cellular Biology
JF - Molecular and Cellular Biology
SN - 0270-7306
IS - 1
ER -