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 ionizing radiation-induced DNA damage and for the initiation of meiotic recombination. Sequence analysis has revealed homology between Mre11 and SbcD, the catalytic subunit of an Escherichia coli enzyme with endo- and exonuclease activity, SbcCD. In this study, the purified Mre11 protein was found to have single-stranded endonuclease activity. This activity was absent from mutant proteins containing single amino acid substitutions in either one of two sequence motifs that are shared by Mre11 and SbcD. Mutants with allele mre11-D56N or mre11-H125N were partially sensitive to ionizing radiation but lacked the other mitotic phenotypes of poor vegetative growth, hyperrecombination, defective nonhomologous end joining, and shortened telomeres that are characteristic of the mre11 null mutant. Diploids homozygous for the mre11-H125N mutation failed to sporulate and accumulated unresected double-strand 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 Spo11-bound DSBs in meiotic cells.
Moreau
S
S
Institute of Cancer Research and Department of Microbiology, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA.
Ferguson
J R
JR
Symington
L S
LS
D000595:Amino Acid Sequence; D000818:Animals; D000071877:Checkpoint Kinase 1; D004260:DNA Repair; D004706:Endodeoxyribonucleases; D004720:Endonucleases / Q000235:genetics / Q000378:metabolism*; D005090:Exodeoxyribonucleases; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008540:Meiosis; D008969:Molecular Sequence Data; D016296:Mutagenesis; D011494:Protein Kinases / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins; D016615:Telomere
D005656:Fungal Proteins; D029701:Saccharomyces cerevisiae Proteins; D011494:Protein Kinases; D000071877:Checkpoint Kinase 1; D004706:Endodeoxyribonucleases; D004720:Endonucleases; D005090:Exodeoxyribonucleases; C094191:MRE11 protein, S cerevisiae