The nuclease activity of Mre11 is required for meiosis but not for mating type switching, end joining, or telomere maintenance

The Saccharomyces cerevisiae MRE11 gene is required for the repair of ioniz ing radiation-induced DNA damage and for the initiation of meiotic recombin ation. Sequence analysis has revealed homology between Mre11 and SbcD, the catalytic subunit of an Escherichia coli enzyme with endo and exonuclease a ctivity, SbcCD. In this study, the purified Mre11 protein was found to have single-stranded endonuclease activity. This activity was absent from mutan t proteins containing single amino acid substitutions in either one of two sequence motifs that are shared by Mre11 and SbcD. Mutants with allele mre1 1-D56N or mre11-H125N were partially sensitive to ionizing radiation but la cked the other mitotic phenotypes of poor vegetative growth, hyperrecombina tion, defective nonhomologous end joining, and shortened telomeres that are characteristic of the mre11 null mutant. Diploids homozygous for the mre11 -H125N mutation failed to spornlate and accumulated unresected double-stran d breaks (DSB) during meiosis. We propose that in mitotic cells DSBs can be processed by other nucleases that are partially redundant with Mre11, but these activities are unable to process Spell-bound DSBs in meiotic cells.