Molecular Cartography: Mapping the Landscape of Meiotic Recombination

Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America.
PLoS Biology (Impact Factor: 9.34). 01/2008; 5(12):e333. DOI: 10.1371/journal.pbio.0050333
Source: PubMed


Mapping recombination hot and cold spots in yeast has previously relied on mutants, which themselves distort the map. Now a new method promises to overcome that problem.

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    • "Rates of HR vary across chromosomes creating regions of recombination hotspots and coldspots (CROMIE et al. 2007; PAN AND KEENEY 2007; LUDIN et al. 2008; LICHTEN AND DE MASSY 2011). A variety of determinants govern hotspot formation, including transcriptional promoters, nucleosome-depleted regions, and histone modifications (WU AND LICHTEN 1994; PAN et al. 2011; SMAGULOVA et al. 2011; MARTIN-CASTELLANOS et al. 2013; CHOI AND HENDERSON 2015). "
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    ABSTRACT: Meiotic homologous recombination (HR) is not uniform across eukaryotic genomes, creating regions of HR hot- and coldspots. Previous study reveals that the Spo11 homolog Rec12 responsible for initiation of meiotic double-strand breaks (DSBs) in the fission yeast Schizosaccharomyces pombe is not targeted to Tf2 retrotransposons. However, whether Tf2s are HR coldspots is not known. Here, we show that the rates of HR across Tf2s are similar to a genome average but substantially increase in mutants deficient for the CENP-B homologs. Abp1, which is the most prominent of the CENP-B family members and acts as the primary determinant of HR suppression at Tf2s, is required to prevent gene conversion and maintain proper recombination exchange of homologous alleles flanking Tf2s. In addition, Abp1-mediated suppression of HR at Tf2s requires all three of its domains with distinct functions in transcriptional repression and higher-order genome organization. We demonstrate that HR suppression of Tf2s can be robustly maintained despite disruption to chromatin factors essential for transcriptional repression and nuclear organization of Tf2s. Intriguingly, we uncover a surprising cooperation between the histone methyltransferase Set1 responsible for histone H3 lysine 4 methylation and the non-homologous end joining pathway in ensuring the suppression of HR at Tf2s. Our study identifies a molecular pathway involving functional cooperation between a transcription factor with epigenetic regulators and DNA repair pathway to regulate meiotic recombination at interspersed repeats.
    Full-text · Article · Sep 2015 · Genetics
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    ABSTRACT: Regulation of meiotic recombination by a multifunctional ATF/CREB protein
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    ABSTRACT: Meiotic recombination shuffles the genome, so each generation inherits a new combination of parental traits. Combining traditional and modern approaches, new work pinpoints where recombination occurs genome-wide.
    Full-text · Article · Jul 2008 · Nature
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