title: Meiosis-specific DNA double-strand breaks are catalyzed by Spo11, a member of a widely conserved protein family.
abstract: Meiotic recombination in S. cerevisiae is initiated by double-strand breaks (DSBs). In certain mutants, breaks accumulate with a covalently attached protein, suggesting that cleavage is catalyzed by the DSB-associated protein via a topoisomerase-like transesterase mechanism. We have purified these protein-DNA complexes and identified the protein as Spo11, one of several proteins required for DSB formation. These findings strongly implicate Spo11 as the catalytic subunit of the meiotic DNA cleavage activity. This is the first identification of a biochemical function for any of the gene products involved in DSB formation. Spo11 defines a protein family with other members in fission yeast, nematodes, and archaebacteria. The S. pombe homolog, rec12p, is also known to be required for meiotic recombination. Thus, these findings provide direct evidence that the mechanism of meiotic recombination initiation is evolutionarily conserved.
authors.affiliation: Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
authors.forename: S
authors.initials: S
authors.lastname: Keeney
authors.forename: C N
authors.initials: CN
authors.lastname: Giroux
authors.forename: N
authors.initials: N
authors.lastname: Kleckner
mesh_terms: D000595:Amino Acid Sequence; D002384:Catalysis; D017124:Conserved Sequence; D004247:DNA / Q000302:isolation & purification / Q000378:metabolism*; D004249:DNA Damage; D004271:DNA, Fungal / Q000302:isolation & purification / Q000378:metabolism*; D005656:Fungal Proteins / Q000235:genetics* / Q000302:isolation & purification / Q000494:pharmacology*; D008540:Meiosis / Q000235:genetics*; D008969:Molecular Sequence Data; D011485:Protein Binding / Q000235:genetics; D011489:Protein Denaturation; D012441:Saccharomyces cerevisiae / Q000235:genetics*
chemical_list: D004271:DNA, Fungal; D005656:Fungal Proteins; D004247:DNA