The C. elegans
p53 homologue CEP-1 embodies structural and functional properties similar to all three vertebrate
p53 family members. The roles of CEP-1 in cell cycle arrest and apoptosis have been previously characterized, however, its role in DNA repair is not known. Loss of
cep-1 results in a mild X chromosome non-disjunction phenotype and increased sensitivity to replication inhibitors, suggesting a potential role in meiotic chromosome segregation and DNA repair. To determine how CEP-1 regulates these processes, we examined its genetic interaction with mutants that have chromosome segregation defects. Ablation of
cep-1 significantly enhanced lethality in the meiotic mutant
him-5 (high incidence of males-5).
cep-1;
him-5 mutants also have abnormal chromosome morphology that is strikingly similar to that observed when
brc-2 and
rad-51 are mutated. We also observed reduced recombination frequencies in
cep-1;
him-5 mutants in comparison to wild-type worms,
cep-1 or
him-5 mutants. These results suggest a cooperative role for CEP-1 and HIM-5 in promoting meiotic recombination. We are currently determining the mechanism by which CEP-1 promotes meiotic recombinational repair and hypothesize that CEP-1 regulates the expression or function of one or more DNA repair proteins. Similar to
cep-1, the mild meiotic defects observed when the Brca1 homologue
brc-1 is mutated are significantly enhanced with the combined loss of
him-5.We observed 60-80% lethality in the progeny of
brc-1;
him-5 mutants but loss of
cep-1 did not enhance the lethality of
brc-1 mutants.There is also no significant difference between the lethality of
cep-1;
brc-1;
him-5 triple mutants and
brc-1;
him-5 double mutants, suggesting that
brc-1 and
cep-1 likely function in the same genetic pathway to promote meiotic recombination. In addition,
brc-1;
him-5 mutants also have chromosomal abnormalities. Our data suggest that CEP-1 and BRC-1 cooperate with HIM-5 to promote meiotic recombinational repair.