Fanconi anemia (FA) is an autosomal recessive syndrome characterized by developmental abnormalities, hypersensitivity to DNA crosslinking agents, chromosome instability, and cancer susceptibility. FA has at least 11 complementation group(A,B,C,D1,D2,E,F,G,I,J,L). FA proteins (A/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. We have investigated the role of a FANCD2 homologue in Caenohabditis elegans
fcd-2(Y41E3.9), which is the only one conserved in C. elegans among the 11 FA proteins. FCD-2 is immunolocalized in the cytosol of germ cells, oocytes, sperms, embryonic cells. RNAi of
fcd-2 induced phenotypes such as DTC-migration defects, bag of worms, defective yolk protein uptake by coelomocytes. When DNA replication was inhibited by hydroxyurea treatment, aberrant small condensed chromosomes were observed in
fcd-2(RNAi) gonads, suggesting
fcd-2 takes part in the replication checkpoint. RNAi of
fcd-2 attenuated induction of apoptosis in the C. elegans germline and resulted in lower embryonic lethality after irradiation with UV or -rays. We are currently investigating the phenotypes of
fcd-2(
tm1298) mutant and the mechanism how deficiency of
fcd-2 leads to a lower sensitivity to DNA damages, as measured by embryonic hatching rate.