BLM Helicase Ortholog Sgs1 Is a Central Regulator of Meiotic Recombination Intermediate Metabolism

Muyt, Arnaud De; Jessop, Lea; Kolar, Elizabeth; Sourirajan, Anuradha; Chen, Jianhong; Dayani, Yaron; Lichten, Michael

doi:10.1016/j.molcel.2012.02.020

Cited by 244 publications

(435 citation statements)

References 67 publications

(115 reference statements)

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“…At HIS4, where MutLg predominates, ssn mutants still display a modest reduction in VDE-initiated COs when MutLg is active, but an even greater relative reduction in the absence of MutLg. These findings are consistent with previous studies suggesting that, in the absence of MutLg, SSNs serve as a back-up that resolves JMs to produce both COs and NCOs (Argueso et al, 2004;De Muyt et al, 2012;Zakharyevich et al, 2012). Our current data indicate that the converse may also be true, since at URA3, MutLg appears to make a greater contribution to CO formation in the absence of SSNs than in their presence.…”

Section: The Interplay Of Resolvase Activities Is Chromosome Context-supporting

confidence: 93%

“…These slower-migrating species contain branched DNA molecules, as would be expected for unresolved joint molecules (D. M., unpublished observations). Steady state VDE-DSB and final NCO levels were similar in all strains ( Figure 3D, Figure 3figure supplement 1), indicating that resolvases do not act during the initial steps of DSB repair, and consistent with most meiotic NCOs forming by mechanisms that do not involve Holliday junction resolution (Allers and Lichten, 2001a;De Muyt et al, 2012;Sourirajan and Lichten, 2008;Zakharyevich et al, 2012).…”

Section: Mutlg Makes Different Contributions To Vde-initiated Co Formmentioning

confidence: 68%

“…MutLg does not appear to make significant contributions to mitotic COs (Ira et al, 2003). A minority of events form ZMM-independent JMs that are resolved as both COs and NCOs by the structure-selective nucleases (SSNs) Mus81-Mms4, Yen1, and Slx1-Slx4, which are responsible for most JM resolution during mitosis (Argueso et al, 2004;Santos et al, 2003;De Muyt et al, 2012;Ho et al, 2010;Muñoz-Galván et al, 2012;Zakharyevich et al, 2012; reviewed by Wyatt and West, 2014). A similar picture, with MutLg forming most meiotic COs and SSNs playing a minor role, is observed in several other eukaryotes (Berchowitz et al, 2007;Holloway et al, 2008;Plug et al, 1998).…”

Section: Introductionmentioning

confidence: 99%

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Local chromosome context is a major determinant of crossover pathway biochemistry during budding yeast meiosis

Medhi¹,

Goldman

Lichten³

2016

Preprint

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The budding yeast genome contains regions where meiotic recombination initiates more frequently than in others. This pattern parallels enrichment for the meiotic chromosome axis proteins Hop1 and Red1. These proteins are important for Spo11-catalyzed double strand break formation; their contribution to crossover recombination remains undefined. Using the sequencespecific VMA1-derived endonuclease (VDE) to initiate recombination in meiosis, we show that chromosome structure influences the choice of proteins that resolve recombination intermediates to form crossovers. At a Hop1-enriched locus, most VDE-initiated crossovers, like most Spo11-initiated crossovers, required the meiosis-specific MutLg resolvase. In contrast, at a locus with lower Hop1 occupancy, most VDE-initiated crossovers were MutLg-independent. In pch2 mutants, the two loci displayed similar Hop1 occupancy levels, and VDE-induced crossovers were similarly MutLg-dependent. We suggest that meiotic and mitotic recombination pathways coexist within meiotic cells, and that features of meiotic chromosome structure determine whether one or the other predominates in different regions.

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Section: The Interplay Of Resolvase Activities Is Chromosome Context-supporting

confidence: 93%

Section: Mutlg Makes Different Contributions To Vde-initiated Co Formmentioning

confidence: 68%

Section: Introductionmentioning

confidence: 99%

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Local chromosome context is a major determinant of crossover pathway biochemistry during budding yeast meiosis

Medhi¹,

Goldman

Lichten³

2016

Preprint

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“…The products are analyzed by two‐dimensional gel electrophoresis and probed to identify DSBs, joint molecules—both interhomolog and intersister, crossover and non‐crossover products 11, 22. This method circumvents the issue of spore viability and has been used to study meiotic mutants with severe viability defects 10, 14, 15, 16, 23, 24, 25. But this method also has the limitation of reporting data of only one locus.…”

Section: Conventional Methods For Analysis Of Meiotic Recombination Imentioning

confidence: 99%

“…If the strand invasion is stabilized by the ZMM proteins (Zip1, Zip2, Zip3, Zip4, Mer3, Msh4, Msh5 and Spo16), it may be extended further by repair synthesis using the homolog and capture the second end of the DSB and form double Holliday junction 6. Biased resolution of these double Holliday junctions facilitated by the ZMM, STR (Sgs1, Top3, Rmi1), Exo1 and the Mlh1‐Mlh3 endonuclease leads to crossovers 7, 8, 9, 10, 11, 12, 13, 14. These class I crossovers show interference—a phenomena where the occurrence of a crossover event in a genetic interval makes it less likely for crossovers to occur in adjacent intervals.…”

Section: Introductionmentioning

confidence: 99%

Genome wide analysis of meiotic recombination in yeast: For a few SNPs more

et al. 2018

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Diploid organisms undergo meiosis to produce haploid germ cells. Crossover events during meiosis promote genetic diversity and facilitate accurate chromosome segregation. The baker's yeast Saccharomyces cerevisiae is extensively used as a model for analysis of meiotic recombination. Conventional methods for measuring recombination events in S. cerevisiae have been limited by the number and density of genetic markers. Next generation sequencing (NGS)‐based analysis of hybrid yeast genomes bearing thousands of heterozygous single nucleotide polymorphism (SNP) markers has revolutionized analysis of meiotic recombination. By facilitating analysis of marker segregation in the whole genome with unprecedented resolution, this method has resulted in the generation of high‐resolution recombination maps in wild‐type and meiotic mutants. These studies have provided novel insights into the mechanism of meiotic recombination. In this review, we discuss the methodology, challenges, insights and future prospects of using NGS‐based methods for whole genome analysis of meiotic recombination. The objective is to facilitate the use of these high through‐put sequencing methods for the analysis of meiotic recombination given their power to provide significant new insights into the process. © 2018 The Authors. IUBMB Life published by Wiley Periodicals, Inc. on behalf of International Union of Biochemistry and Molecular Biology, 70(8):743–752, 2018

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Bloom syndrome helicase in meiosis: Pro‐crossover functions of an anti‐crossover protein

Hatkevich

Sekelsky

2017

BioEssays

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The functions of the Bloom syndrome helicase (BLM) and its orthologs are well characterized in mitotic DNA damage repair, but their roles within the context of meiotic recombination are less clear. In meiotic recombination, multiple repair pathways are used to repair meiotic DSBs, and current studies suggest that BLM may regulate the use of these pathways. Based on literature from S. cerevisiae, A. thaliana, M. musculus, D. melanogaster, and C. elegans, we present a unified model for a critical meiotic role of BLM and its orthologs. In this model, BLM and its orthologs utilize helicase activity to regulate the use of various pathways in meiotic recombination by continuously disassembling recombination intermediates. This unwinding activity provides the meiotic program with a steady pool of early recombination substrates, increasing the probability for a DSB to be processed by the appropriate pathway. As a result of BLM activity, crossovers are properly placed throughout the genome, promoting proper chromosomal disjunction at the end of meiosis. This unified model can be used to further refine the complex role of BLM and its orthologs in meiotic recombination.

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BLM Helicase Ortholog Sgs1 Is a Central Regulator of Meiotic Recombination Intermediate Metabolism

Cited by 244 publications

References 67 publications

Local chromosome context is a major determinant of crossover pathway biochemistry during budding yeast meiosis

Local chromosome context is a major determinant of crossover pathway biochemistry during budding yeast meiosis

Genome wide analysis of meiotic recombination in yeast: For a few SNPs more

Bloom syndrome helicase in meiosis: Pro‐crossover functions of an anti‐crossover protein

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