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      Resolving complex chromosome structures during meiosis: versatile deployment of Smc5/6

      Chromosoma
      Springer
      structural maintenance of chromosomes, smc5/6, meiosis, meiotic recombination, dna repair

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          Abstract

          The Smc5/6 complex, along with cohesin and condensin, is a member of the structural maintenance of chromosome (SMC) family, large ring-like protein complexes that are essential for chromatin structure and function. Thanks to numerous studies of the mitotic cell cycle, Smc5/6 has been implicated to have roles in homologous recombination, restart of stalled replication forks, maintenance of ribosomal DNA (rDNA) and heterochromatin, telomerase-independent telomere elongation, and regulation of chromosome topology. The nature of these functions implies that the Smc5/6 complex also contributes to the profound chromatin changes, including meiotic recombination, that characterize meiosis. Only recently, studies in diverse model organisms have focused on the potential meiotic roles of the Smc5/6 complex. Indeed, Smc5/6 appears to be essential for meiotic recombination. However, due to both the complexity of the process of meiosis and the versatility of the Smc5/6 complex, many additional meiotic functions have been described. In this review, we provide a clear overview of the multiple functions found so far for the Smc5/6 complex in meiosis. Additionally, we compare these meiotic functions with the known mitotic functions in an attempt to find a common denominator and thereby create clarity in the field of Smc5/6 research.

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          Most cited references94

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          Postreplicative recruitment of cohesin to double-strand breaks is required for DNA repair.

          Chromosome stability depends on accurate chromosome segregation and efficient DNA double-strand break (DSB) repair. Sister chromatid cohesion, established during S phase by the protein complex cohesin, is central to both processes. In the absence of cohesion, chromosomes missegregate and G2-phase DSB repair fails. Here, we demonstrate that G2-phase repair also requires the presence of cohesin at the damage site. Cohesin components are shown to be recruited to extended chromosome regions surrounding DNA breaks induced during G2. We find that in the absence of functional cohesin-loading proteins (Scc2/Scc4), the accumulation of cohesin at DSBs is abolished and repair is defective, even though sister chromatids are connected by S phase generated cohesion. Evidence is also provided that DSB induction elicits establishment of sister chromatid cohesion in G2, implicating that damage-recruited cohesin facilitates DNA repair by tethering chromatids.
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            A SUMO ligase is part of a nuclear multiprotein complex that affects DNA repair and chromosomal organization.

            Through a genetic screen using myosin-like protein strains mlp1Delta mlp2Delta and biochemical purification, we identified a complex of eight proteins, each required for growth and DNA repair in Saccharomyces cerevisiae. Among the subunits are Mms21 that contains a putative Siz/PIAS (protein inhibitor of activated signal transducer and activator of transcription) RING domain characteristic of small ubiquitin-like modifier (SUMO) ligases, two structural-maintenance-of-chromosome (Smc) proteins, Smc5 and Smc6, and a protein that contains an ubiquitin ligase signature domain. We show that these proteins colocalized to several distinct nuclear foci. Biochemical and genetic data demonstrated that Mms21 indeed functions as a SUMO ligase and that this activity requires the Siz/PIAS (protein inhibitor of activated signal transducer and activator of transcription) RING domain. The substrates for this SUMO ligase include a subunit of the octameric complex, Smc5, and the DNA repair protein Yku70. We further show that the abolition of the SUMO E3 activity of Mms21 leads to such disparate phenotypes as DNA damage sensitivity, defects in nucleolar integrity and telomere clustering, silencing, and length regulation. We propose that Mms21 sumoylates proteins involved in these diverse processes and that the other members of the complex, particularly Smc5/6, facilitate proper substrate sumoylation by localizing Mms21 to specific chromosomal regions.
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              DNA damage response pathway uses histone modification to assemble a double-strand break-specific cohesin domain.

              The postreplicative repair of double-strand breaks (DSBs) is thought to require sister chromatid cohesion, provided by the cohesin complex along the chromosome arms. A further specialized role for cohesin in DSB repair is suggested by its de novo recruitment to regions of DNA damage in mammals. Here, we show in budding yeast that a single DSB induces the formation of a approximately 100 kb cohesin domain around the lesion. Our analyses suggest that the primary DNA damage checkpoint kinases Mec1p and Tel1p phosphorylate histone H2AX to generate a large domain, which is permissive for cohesin binding. Cohesin binding to the phospho-H2AX domain is enabled by Mre11p, a component of a critical repair complex, and Scc2p, a component of the cohesin loading machinery that is necessary for sister chromatid cohesion. We also provide evidence that the DSB-induced cohesin domain functions in postreplicative repair.
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                Author and article information

                Journal
                25947290
                4761004
                10.1007/s00412-015-0518-9
                This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

                Genetics
                structural maintenance of chromosomes,smc5/6,meiosis,meiotic recombination,dna repair
                Genetics
                structural maintenance of chromosomes, smc5/6, meiosis, meiotic recombination, dna repair

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