C-elegans mre-11 is required for meiotic recombination and DNA repair but is dispensable for the meiotic G(2) DNA damage checkpoint

We investigated the roles of Caenorhabditis elegans MRE-11 in multiple cell ular processes required to maintain genome integrity. Although yeast Mre11 is known to promote genome stability through several diverse pathways, invi ability of vertebrate cells that lack Mre11 has hindered elucidation of the in vivo roles of this conserved protein in metazoan biology. Worms homozyg ous for an mre-11 null mutation are viable, allowing us to demonstrate in v ivo requirements for MRE-11 in meiotic recombination and DNA repair. In mre -11 mutants, meiotic crossovers are not detected, and oocyte chromosomes la ck chiasmata but appear otherwise intact, gamma -irradiation of mre-11 muta nt germ cells during meiotic prophase eliminates progeny survivorship and i nduces chromosome fragmentation and other cytologically visible abnormaliti es, indicating a defect in repair of radiation-induced chromosome damage. W hereas mre-11 mutant germ cells are repair-deficient, they retain function of the meiotic G(2) DNA damage checkpoint that triggers germ cell apoptosis in response to ionizing radiation. Although mre-11/mre-11 animals derived from heterozygous parents are viable and produce many embryos, there is a m arked drop both in the number and survivorship of embryos produced by succe eding generations. This progressive loss of fecundity and viability indicat es that MRE-11 performs a function essential for maintaining reproductive c apacity in the species.