ATM (ataxia telangiectasia mutated gene)-like gene and Chk2 -like gene were identified in the genome of C. elegans . The putative products of the genes, termed
Ce-atl-1 ( C. elegans ATM-like 1 ) and
Ce-chk-2 consist of 2514 and 450 amino acid residues, respectively. The C-terminal sequence of
Ce-atl-1 , which contains a PI-3 kinase like domain, showed good homology with the products of the gene MEC1/ESR1 from budding yeast, the
rad3+ gene of fission yeast and mammalian ATR genes. The sequence of
Ce-chk-2 product shows 34.3% identity over 449 residues to human Chk2. To study the function of the
Ce-atl-1 and
Ce-chk-2 genes, we carried out RNA interference (RNAi) experiments to repress its expression. The results of RNAi indicated that the major phenotype associated with repression of
Ce-atl-1 was lethality (approximately 20-50%) during early embryogenesis. Among the surviving progeny, males (XO animals) arose at a high frequency (2-30%). In addition, 5% of oocyte chromosomes demonstrated aneuploidy due to a defect in pre-meiotic chromosomal segregation. We also observed other variable phenotypes among the surviving F1 and F2 animals; namely, lethal morphological abnormalities in L1-L2 larvae, protruding vulvae, abnormal gonads, irregular oocytes, dumpy (Dpy) or small-sized (Sma) adults, and bursting of the vulva, but these phenotypes were not passed on to the next generation. The sensitivity to genotoxin (UV and X-ray irradiation) was also increased by the repression of
Ce-atl-1 gene. However, the phenotype of repression of
Ce-chk-2 gene was completely difference from that of
Ce-atl-1 .
Ce-chk-2 gene was dispensable for repair process of DNA double strand breaks, but essential for meiotic process such as chiasma formation and meiotic chromosome synapses. These observations indicate that
Ce-atl-1 acts as a monitoring enzyme for DNA damage checkpoint control, but
Ce-chk-2 does not, although Chk2 of yeast and mammals functions as a downstream kinase of ATM family in checkpoint control.