We have isolated and analyzed mutants defective in the nematode ortholog of yeast MRE11, a multifunctional protein with roles in diverse cellular processes required to maintain genome integrity, including meiotic recombination, DNA repair, and telomere length maintenance. While MRE11 is highly conserved among several species and has been linked to genetic disease in humans, exploration of its in vivo roles in metazoan systems has been hampered by the fact that vertebrate cells that lack MRE11 are inviable. We have found that worms homozygous for an
mre-11 null mutation are viable, allowing us to demonstrate an in vivo requirement for MRE-11 in meiotic recombination and DNA repair. In
mre-11 mutants, crossovers are not detected and chromosomes lack chiasmata at diakinesis but appear otherwise intact. Irradiation of
mre-11 mutants not only fails to induce chiasmata but also eliminates progeny survivorship and leads to cytologically visible chromosomal abnormalities including fragmentation. These results indicate a defect in the ability of
mre-11 mutant germ cells to repair radiation-induced damage. While they are repair-deficient, we show that
mre-11 mutant germ cells retain function of the meiotic G2 DNA damage checkpoint. Although
mre-11 homozyogtes derived from heterozygous parents are fully viable and produce a normal number of embryos, there is a marked drop both in the number and in the survivorship of embryos produced by succeeding generations. As a result, the strain cannot be propagated as a homozygous stock. This progressive loss of fecundity and viability sets
mre-11 mutants apart from many other meiotic recombination-defective mutants, and indicates that MRE-11 performs an additional essential function in maintaining reproductive capacity in the species.