Homologue engagement controls meiotic DNA break number and distribution Journal Article


Authors: Thacker, D.; Mohibullah, N.; Zhu, X.; Keeney, S.
Article Title: Homologue engagement controls meiotic DNA break number and distribution
Abstract: Meiotic recombination promotes genetic diversification as well as pairing and segregation of homologous chromosomes, but the double-strand breaks (DSBs) that initiate recombination are dangerous lesions that can cause mutation or meiotic failure. How cells control DSBs to balance between beneficial and deleterious outcomes is not well understood. Here we test the hypothesis that DSB control involves a network of intersecting negative regulatory circuits. Using multiple complementary methods, we show that DSBs form in greater numbers in Saccharomyces cerevisiae cells lacking ZMM proteins, a suite of recombination-promoting factors traditionally regarded as acting strictly downstream of DSB formation. ZMM-dependent DSB control is genetically distinct from a pathway tying break formation to meiotic progression through the Ndt80 transcription factor. These counterintuitive findings suggest that homologous chromosomes that have successfully engaged one another stop making breaks. Genome-wide DSB maps uncover distinct responses by different subchromosomal domains to the ZMM mutation zip3 (also known as cst9), and show that Zip3 is required for the previously unexplained tendency of DSB density to vary with chromosome size. Thus, feedback tied to ZMM function contributes in unexpected ways to spatial patterning of recombination. © 2014 Macmillan Publishers Limited.
Keywords: unclassified drug; nonhuman; protein function; chromosome structure; meiosis; complex formation; transcription factor; mutational analysis; saccharomyces cerevisiae; double stranded dna break; oligonucleotide; spo11 protein; regulator protein; meiotic recombination; dna homolog; chromosome size; priority journal; article; protein zmm; transcription factor ndt80
Journal Title: Nature
Volume: 510
Issue: 7504
ISSN: 0028-0836
Publisher: Nature Publishing Group  
Date Published: 2014-06-12
Start Page: 241
End Page: 246
Language: English
DOI: 10.1038/nature13120
PROVIDER: scopus
PMCID: PMC4057310
PUBMED: 24717437
DOI/URL:
Notes: Nature -- Export Date: 8 July 2014 -- CODEN: NATUA -- Source: Scopus
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MSK Authors
  1. Scott N Keeney
    111 Keeney
  2. Xuan Zhu
    7 Zhu