title: Reduced Crossover Interference and Increased ZMM-Independent Recombination in the Absence of Tel1/ATM.
abstract: Meiotic recombination involves the repair of double-strand break (DSB) precursors as crossovers (COs) or noncrossovers (NCOs). The proper number and distribution of COs is critical for successful chromosome segregation and formation of viable gametes. In budding yeast the majority of COs occurs through a pathway dependent on the ZMM proteins (Zip2-Zip3-Zip4-Spo16, Msh4-Msh5, Mer3), which form foci at CO-committed sites. Here we show that the DNA-damage-response kinase Tel1/ATM limits ZMM-independent recombination. By whole-genome mapping of recombination products, we find that lack of Tel1 results in higher recombination and reduced CO interference. Yet the number of Zip3 foci in tel1Δ cells is similar to wild type, and these foci show normal interference. Analysis of recombination in a tel1Δ zip3Δ double mutant indicates that COs are less dependent on Zip3 in the absence of Tel1. Together these results reveal that in the absence of Tel1, a significant proportion of COs occurs through a non-ZMM-dependent pathway, contributing to a CO landscape with poor interference. We also see a significant change in the distribution of all detectable recombination products in the absence of Tel1, Sgs1, Zip3, or Msh4, providing evidence for altered DSB distribution. These results support the previous finding that DSB interference depends on Tel1, and further suggest an additional level of DSB interference created through local repression of DSBs around CO-designated sites.
authors: Department of Obstetrics, Gynecology, and Reproductive Sciences and Center for Reproductive Sciences, University of California, San Francisco, San Francisco, California, United States of America.
authors: Carol M
authors: CM
authors: Anderson
authors: Department of Obstetrics, Gynecology, and Reproductive Sciences and Center for Reproductive Sciences, University of California, San Francisco, San Francisco, California, United States of America.
authors: Ashwini
authors: A
authors: Oke
authors: Department of Obstetrics, Gynecology, and Reproductive Sciences and Center for Reproductive Sciences, University of California, San Francisco, San Francisco, California, United States of America.
authors: Phoebe
authors: P
authors: Yam
authors: Department of Obstetrics, Gynecology, and Reproductive Sciences and Center for Reproductive Sciences, University of California, San Francisco, San Francisco, California, United States of America.
authors: Tangna
authors: T
authors: Zhuge
authors: Department of Obstetrics, Gynecology, and Reproductive Sciences and Center for Reproductive Sciences, University of California, San Francisco, San Francisco, California, United States of America.
authors: Jennifer C
authors: JC
authors: Fung
mesh_terms: D003434:Crossing Over, Genetic; D004265:DNA Helicases / Q000502:physiology; D004268:DNA-Binding Proteins / Q000502:physiology; D055786:Gene Knockout Techniques; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008869:Microtubule-Associated Proteins / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D011995:Recombination, Genetic; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000502:physiology; D044767:Ubiquitin-Protein Ligases / Q000502:physiology
chemical_list: D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; C091158:MSH4 protein, S cerevisiae; C094801:MSH5 protein, S cerevisiae; D008869:Microtubule-Associated Proteins; D029701:Saccharomyces cerevisiae Proteins; C527704:Spo16 protein, S cerevisiae; D044767:Ubiquitin-Protein Ligases; D017346:Protein Serine-Threonine Kinases; C513623:TEL1 protein, S cerevisiae; C455499:HFM1 protein, S cerevisiae; D004265:DNA Helicases; C523917:Zip3 protein, S cerevisiae