Meiotic double-strand breaks occur once per pair of (sister) chromatids and, via Mec1/ATR and Tel1/ATM, once per quartet of chromatids

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 108; no. 50; pp. 20036 - 20041
• Main Authors: Zhang, Liangran, Kleckner, Nancy E, Storlazzi, Aurora, Kim, Keun P
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 13.12.2011; National Acad Sciences
• Subjects: Binomial distributions; Biological Sciences; Cell division; Chromatids; Chromatids - metabolism; Chromosomes; Crossovers; DNA Breaks, Double-Stranded; Genetic loci; Genotype & phenotype; Homeostasis; Hot spots; Intracellular Signaling Peptides and Proteins - metabolism; Kinases; Meiosis; Memory interference; Models, Genetic; mutants; Mutation; Mutation - genetics; Nuclear interactions; Nuclei; phenotype; Protein-Serine-Threonine Kinases - metabolism; Recombination; Recombination, Genetic - genetics; Saccharomyces cerevisiae - cytology; Saccharomyces cerevisiae - enzymology; Saccharomyces cerevisiae Proteins - metabolism; Signal transduction; sister chromatids; spatial distribution; Spreading; Tetrads; Yeasts
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.1117937108

Meiotic recombination initiates via programmed double-strand breaks (DSBs). We investigate whether, at a given initiation site, DSBs occur independently among the four available chromatids. For a single DSB "hot spot", the proportions of nuclei exhibiting zero, one, or two (or more) observable events were defined by tetrad analysis and compared with those predicted by different DSB distribution scenarios. Wild-type patterns are incompatible with independent distribution of DSBs among the four chromatids. In most or all nuclei, DSBs occur one-per-pair of chromatids, presumptively sisters. In many nuclei, only one DSB occurs per four chromatids, confirming the existence of trans inhibition where a DSB on one chromosome interactively inhibits DSB formation on the partner chromosome. Several mutants exhibit only a one-per-pair constraint, a phenotype we propose to imply loss of trans inhibition. Signal transduction kinases Mec1 (ATR) and Tel1 (ATM) exhibit this phenotype and thus could be mediators of this effect. Spreading trans inhibition can explain even spacing of total recombinational interactions and implies that establishment of interhomolog interactions and DSB formation are homeostatic processes. The two types of constraints on DSB formation provide two different safeguards against recombination failure during meiosis.