Disjunction of Homologous Chromosomes in Meiosis I Depends on Proteolytic Cleavage of the Meiotic Cohesin Rec8 by Separin

Buonomo, Sara B.C.; Clyne, Rosemary; Fuchs, Joerg; Loidl, Josef; Uhlmann, Frank; Nasmyth, Kim

doi:10.1016/s0092-8674(00)00131-8

Cited by 411 publications

(387 citation statements)

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“…Paradoxically, in meiosis cells intentionally introduce dsDNA breaks into their chromosomes to induce the rate of homologous recombination about three orders of magnitude, relative to the rate in mitotic cells (reviewed in Lichten, 2001). Meiotic recombination increases genetic diversity and produces crossovers which function cooperatively with sister chromatid cohesion to ensure the faithful segregation of chromosomes in the first meiotic division (Krawchuk et al, 1999;Buonomo et al, 2000;Kitajima et al, 2004;Rabitsch et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

A DNA binding motif of meiotic recombinase Rec12 (Spo11) defined by essential glycine-202, and persistence of Rec12 protein after completion of recombination

DeWall¹,

Davidson²,

Sharif³

et al. 2005

Gene

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The Rec12 (Spo11) protein of the fission yeast Schizosaccharomyces pombe is a meiosis-specific ortholog of the catalytic subunit of type VI topoisomerases and is thought to catalyze doublestrand DNA breaks that initiate recombination. We tested the hypothesis that the rec12-117 allele affects the choice of pathways by which recombination is resolved. DNA sequence analysis revealed a single missense mutation in the coding region (rec12-G202E). The corresponding glycine-202 residue of Rec12 protein is strictly conserved in proteins of the Rec12/Spo11/Top6A family. It maps to the base of the DNA binding pocket in the crystal structure of the archaeal ortholog, Top6A. The rec12-G202E mutants lacked crossover and non-crossover recombination, demonstrating that rec12-G202E does not affect choice of resolution pathway. Like rec12-D15 null mutants, the rec12-G202E mutants suffered chromosome segregation errors in meiosis I. The Rec12-G202E protein was as stable as wild-type Rec12, demonstrating that glycine-202 is essential for a biochemical activity of Rec12 protein, rather than for its stability. These findings suggest that Rec12 facilitates binding of the meiotic recombinase to its substrate, DNA. Interestingly, the bulk of Rec12 protein persisted until the time of anaphase I, and a portion of Rec12 protein persisted until the time of anaphase II, after which it was undetectable. This suggests that Rec12 protein has additional meiotic functions after completion of recombination in prophase, as inferred previously from genetic studies.

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Section: Introductionmentioning

confidence: 99%

A DNA binding motif of meiotic recombinase Rec12 (Spo11) defined by essential glycine-202, and persistence of Rec12 protein after completion of recombination

DeWall¹,

Davidson²,

Sharif³

et al. 2005

Gene

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“…Third, cohesin complexes must be lost in a stepwise manner from chromosomes. During meiosis I cohesin complexes are lost from chromosome arms to bring about the segregation of homologous chromosomes (6). The residual cohesins at centromeres facilitate the accurate segregation of sister chromatids during meiosis II.…”

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confidence: 99%

Polo kinase Cdc5 is a central regulator of meiosis I

Attner

Miller

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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During meiosis, two consecutive rounds of chromosome segregation yield four haploid gametes from one diploid cell. The Polo kinase Cdc5 is required for meiotic progression, but how Cdc5 coordinates multiple cell-cycle events during meiosis I is not understood. Here we show that CDC5-dependent phosphorylation of Rec8, a subunit of the cohesin complex that links sister chromatids, is required for efficient cohesin removal from chromosome arms, which is a prerequisite for meiosis I chromosome segregation. CDC5 also establishes conditions for centromeric cohesin removal during meiosis II by promoting the degradation of Spo13, a protein that protects centromeric cohesin during meiosis I. Despite CDC5's central role in meiosis I, the protein kinase is dispensable during meiosis II and does not even phosphorylate its meiosis I targets during the second meiotic division. We conclude that Cdc5 has evolved into a master regulator of the unique meiosis I chromosome segregation pattern.P olo kinases are central regulators of chromosome segregation and control multiple mitotic events (1). Budding yeast contains a single Polo kinase, CDC5. Unlike in higher eukaryotes, budding yeast CDC5 primarily regulates postmetaphase events, its essential function being to trigger exit from mitosis (2). CDC5 also contributes to the efficient inactivation of cohesins, the protein complexes that hold sister chromatids together until the onset of chromosome segregation. Cdc5 phosphorylates the cohesin subunit Mcd1/Scc1 to facilitate its cleavage by the protease separase (3).CDC5 also regulates the specialized cell division that gives rise to gametes, known as meiosis (4). During meiosis, two consecutive rounds of chromosome segregation follow one round of DNA replication. During meiosis I, homologous chromosomes segregate; during meiosis II, sister chromatids separate (5). The chromosome segregation machinery is modified in three ways to facilitate the unusual meiosis I division. First, the combination of homologous recombination and cohesin complexes distal to the resulting cross-overs mediate the physical linkage of homologous chromosomes, which is essential for their accurate segregation during meiosis I. Second, sister chromatids of each homolog must be segregated to the same pole rather than to opposite poles, as they are during mitosis. The fusion of sister kinetochores by co-orientation factors (the monopolin complex in yeast) facilitates the attachment of microtubules emanating from one spindle pole. Third, cohesin complexes must be lost in a stepwise manner from chromosomes. During meiosis I cohesin complexes are lost from chromosome arms to bring about the segregation of homologous chromosomes (6). The residual cohesins at centromeres facilitate the accurate segregation of sister chromatids during meiosis II. Cdc5 has been implicated in the execution of all three meiosis I-specific events. CDC5 is required for the resolution of double Holliday junctions during homologous recombination (7,8). Cdc5 also controls the co-orientation of ...

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“…The anaphase promoting complex (APC), a multisubunit ubiquitin ligase (King et al 1995;Sudakin et al 1995), targets the anaphase inhibitor Pds1 (securin) for destruction by the proteasome (Cohen-Fix et al 1996). Destruction of Pds1 allows its binding partner, separase (Esp1) to cleave Rec8 in meiosis or Scc1/Mcd1 in mitosis, thus destroying the linkage between sister chromatids (Ciosk et al 1998;Buonomo et al 2000). Despite an active separase, centromeric Rec8 is protected during meiosis I until meiosis II when separase is reactivated and removes Rec8 at the onset of anaphase I.…”

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confidence: 99%