Repair pathways independent of the Fanconi anemia nuclear core complex play a predominant role in mitigating formaldehyde-induced DNA damage.
The role of the Fanconi anemia (FA) repair pathway for DNA damage induced by formaldehyde was examined in the work described here. The following cell types were used: mouse embryonic fibroblast cell lines FANCA(-/-), FANCC(-/-), FANCA(-/-)C(-/-), FANCD2(-/-) and their parental cells, the Chinese hamster cell lines FANCD1 mutant (mt), FANCGmt, their revertant cells, and the corresponding wild-type (wt) cells. Cell survival rates were determined with colony formation assays after formaldehyde treatment. DNA double strand breaks (DSBs) were detected with an immunocytochemical γH2AX-staining assay. Although the sensitivity of FANCA(-/-), FANCC(-/-) and FANCA(-/-)C(-/-) cells to formaldehyde was comparable to that of proficient cells, FANCD1mt, FANCGmt and FANCD2(-/-) cells were more sensitive to formaldehyde than the corresponding proficient cells. It was found that homologous recombination (HR) repair was induced by formaldehyde. In addition, γH2AX foci in FANCD1mt cells persisted for longer times than in FANCD1wt cells. These findings suggest that formaldehyde-induced DSBs are repaired by HR through the FA repair pathway which is independent of the FA nuclear core complex.
Department of Biology, School of Medicine, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521, Japan.
Taichi
T
Noda
Akihisa
A
Takahashi
Natsuko
N
Kondo
Eiichiro
E
Mori
Noritomo
N
Okamoto
Yosuke
Y
Nakagawa
Ken
K
Ohnishi
Małgorzata Z
MZ
Zdzienicka
Larry H
LH
Thompson
Thomas
T
Helleday
Hideo
H
Asada
Takeo
T
Ohnishi
D000818:Animals; D024682:BRCA2 Protein / Q000502:physiology; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D004249:DNA Damage; D004260:DNA Repair / Q000235:genetics*; D004274:DNA, Recombinant; D052217:Fanconi Anemia Complementation Group A Protein / Q000502:physiology; D052218:Fanconi Anemia Complementation Group C Protein / Q000502:physiology; D052236:Fanconi Anemia Complementation Group D2 Protein / Q000502:physiology; D051856:Fanconi Anemia Complementation Group Proteins / Q000502:physiology*; D005557:Formaldehyde / Q000633:toxicity; D006657:Histones / Q000378:metabolism; D051379:Mice
D024682:BRCA2 Protein; D004274:DNA, Recombinant; D052217:Fanconi Anemia Complementation Group A Protein; D052218:Fanconi Anemia Complementation Group C Protein; D052236:Fanconi Anemia Complementation Group D2 Protein; D051856:Fanconi Anemia Complementation Group Proteins; D006657:Histones; C475961:gamma-H2AX protein, mouse; D005557:Formaldehyde