Mutual, spatially limited control of meiotic DNA break formation by Mre11-Rad50-Nbs1 DNA repair complex and Tel1 (ATM) protein kinase.

Meiotic recombination is initiated by DNA double-strand breaks (DSBs); factors that control DSB frequencies are important to produce viable progeny. In many organisms, the ATM (Tel1) protein kinase prevents excessive meiotic DSBs, especially nearby DSBs on the same chromatid. Normally, two close DSBs are less frequent than expected from independence, a feature called DSB interference, which is lost in tel1Δ mutants. In the fission yeast Schizosaccharomyces pombe, high-level DSB formation depends on linear elements, Hop1, and meiotic cohesin complexes; we show here that these complexes impart competition between nearby DSB sites. When these complexes are impaired, Tel1 substantially represses DSB formation, and in its absence, two close DSBs on the same chromatid occur frequently and manifest high negative interference. After mitotic DNA damage, the conserved Mre11-Rad50-Nbs1 (MRN) complex is required for DNA resection, and the Tel1 kinase activity is needed to complete DSB repair. We found that during meiosis mre11Δ and rad50Δ mutants, like tel1Δ mutants, lack DSB interference and display highly negative DSB interference in meiotic complex mutants. Thus, MRN at a DSB site appears critical for Tel1 function in meiosis and reveals a complex interplay of positive and negative factors controlling meiotic DSB formation.