Molecular Cartography: Mapping the Landscape of Meiotic Recombination

Article (PDF Available)inPLoS Biology 5(12):e333 · January 2008with24 Reads
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.
    • "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). "
    [Show abstract] [Hide abstract] 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
    • "Crossover distribution is also regulated in many organisms. For example, crossover formation is suppressed at centromeres and telomeres in budding yeast [24]. It is also known that the single interhomolog crossover is frequently located at the terminal quarters of the autosomes and the terminal thirds of the X chromosome in C. elegans [25,26]. "
    [Show abstract] [Hide abstract] ABSTRACT: The number and distribution of crossover events are tightly regulated at prophase of meiosis I. The resolution of Holliday junctions by structure-specific endonucleases, including MUS-81, SLX-1, XPF-1 and GEN-1, is one of the main mechanisms proposed for crossover formation. However, how these nucleases coordinately resolve Holliday junctions is still unclear. Here we identify both the functional overlap and differences between these four nucleases regarding their roles in crossover formation and control in the Caenorhabditis elegans germline. We show that MUS-81, XPF-1 and SLX-1, but not GEN-1, can bind to HIM-18/SLX4, a key scaffold for nucleases. Analysis of synthetic mitotic defects revealed that MUS-81 and SLX-1, but not XPF-1 and GEN-1, have overlapping roles with the Bloom syndrome helicase ortholog, HIM-6, supporting their in vivo roles in processing recombination intermediates. Taking advantage of the ease of genetic analysis and high-resolution imaging afforded by C. elegans, we examined crossover designation, frequency, distribution and chromosomal morphology in single, double, triple and quadruple mutants of the structure-specific endonucleases. This revealed that XPF-1 functions redundantly with MUS-81 and SLX-1 in executing crossover formation during meiotic double-strand break repair. Analysis of crossover distribution revealed that SLX-1 is required for crossover suppression at the center region of the autosomes. Finally, analysis of chromosome morphology in oocytes at late meiosis I stages uncovered that SLX-1 and XPF-1 promote meiotic chromosomal stability by preventing formation of chromosomal abnormalities. We propose a model in which coordinate action between structure-specific nucleases at different chromosome domains, namely MUS-81, SLX-1 and XPF-1 at the arms and SLX-1 at the center region, exerts positive and negative regulatory roles, respectively, for crossover control during C. elegans meiosis.
    Full-text · Article · Jul 2013
    • "When DBS are repaired there are two possible outcomes, the first one results in exchange of DNA between homologous chromosomes also known as cross-over and the second outcome results in no exchange of genetic information or non-crossover [11]. The process of meiotic recombination is tightly regulated and not all regions of the chromosome are involved in recombination [11]. Any error resulting from improperly repaired DSB may have detrimental effects on the cell. "
    [Show abstract] [Hide abstract] ABSTRACT: In Plasmodium, meiosis occurs in diploid zygotes as they develop into haploid motile ookinetes inside the mosquito. Further sporogonic development involves transformation of ookinetes into oocysts and formation of infective sporozoites. Reverse genetics was employed to examine the role of the meiotic specific recombinase Dmc1, a bacterial RecA homolog during sporogony in Plasmodium berghei. PbDmc1 knockout (KO) parasites showed normal asexual growth kinetics compared to WT parasites; however oocyst formation in mosquitoes was reduced by 50 to 80%. Moreover, the majority of oocysts were retarded in their growth and were smaller in size compared to WT parasites. Only a few Dmc1 KO parasites completed maturation resulting in formation of fewer sporozoites which were incapable of infecting naive mice or hepatocytes in vitro. PbDmc1 KO parasites were shown to be approximately 18 times more sensitive to Bizelesin, a DNA alkylating drug compared to WT parasites as reflected by impairment of oocyst formation and sporogonic development in the mosquito vector. Our findings suggest that PbDmc1 plays a critical role in malaria transmission biology.
    Full-text · Article · Dec 2012
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