The Caenorhabditis elegans FancD2 ortholog is required for survival following DNA damage.
Fanconi anemia (FA) is an autosomal recessive disease characterized by bone-marrow failure, congenital abnormalities, and cancer susceptibility. There are 11 FA complementation groups in human where 8 genes have been identified. We found that FancD2 is conserved in evolution and present in the genome of the nematode Caenorhabditis elegans. The gene Y41E3.9 (CeFancD2) encodes a structural ortholog of human FANCD2 and is composed of 10 predicted exons. Our analysis showed that exons 6 and 7 were absent from a CeFancD2 EST suggesting the presence of a splice variant. In an attempt to characterize its role in DNA damage, we depleted worms of CeFANCD2 using RNAi. When the CeFANCD2(RNAi) worms were treated with a crosslinking agent, a significant drop in the progeny survival was noted. These worms were also sensitive, although to a lesser extent, to ionizing radiation (IR). Therefore, these data support an important role for CeFANCD2 in DNA damage response as for its human counterpart. The data also support the usefulness of C. elegans to study the Fanconi anemia pathway, and emphasize the biological importance of FANCD2 in DNA damage response throughout evolution.
Dequen
Florence
F
CHUL Research Centre, Pediatrics Research Unit and Laval University, Department of Pediatrics, Canada.
St-Laurent
Jean-François
JF
Gagnon
Steve N
SN
Carreau
Madeleine
M
Desnoyers
Serge
S
D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000502:physiology / Q000528:radiation effects; D004249:DNA Damage / Q000235:genetics / Q000502:physiology; D005091:Exons; D052236:Fanconi Anemia Complementation Group D2 Protein; D005720:Gamma Rays; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology / Q000528:radiation effects; D010802:Phylogeny; D034622:RNA Interference / Q000502:physiology / Q000528:radiation effects; D016019:Survival Analysis
C499905:FANCD2 protein, human; D052236:Fanconi Anemia Complementation Group D2 Protein; D009687:Nuclear Proteins