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

Medhi, Darpan; Goldman, Alastair S. H.; Lichten, Michael

doi:10.1101/064519

Cited by 8 publications

(11 citation statements)

References 129 publications

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“…A recent study suggested the importance of the local axis-enriched context to repair DSBs by the interfering CO pathway (Medhi et al 2016). Consistently, our data identified a link between the ZZS complex and the chromosome axis.…”

Section: The Zzs Complex Shepherds Joint Molecules Toward a Pro-co Statesupporting

confidence: 90%

A meiotic XPF–ERCC1-like complex recognizes joint molecule recombination intermediates to promote crossover formation

et al. 2018

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Meiotic crossover formation requires the stabilization of early recombination intermediates by a set of proteins and occurs within the environment of the chromosome axis, a structure important for the regulation of meiotic recombination events. The molecular mechanisms underlying and connecting crossover recombination and axis localization are elusive. Here, we identified the ZZS (Zip2-Zip4-Spo16) complex, required for crossover formation, which carries two distinct activities: one provided by Zip4, which acts as hub through physical interactions with components of the chromosome axis and the crossover machinery, and the other carried by Zip2 and Spo16, which preferentially bind branched DNA molecules in vitro. We found that Zip2 and Spo16 share structural similarities to the structure-specific XPF-ERCC1 nuclease, although it lacks endonuclease activity. The XPF domain of Zip2 is required for crossover formation, suggesting that, together with Spo16, it has a noncatalytic DNA recognition function. Our results suggest that the ZZS complex shepherds recombination intermediates toward crossovers as a dynamic structural module that connects recombination events to the chromosome axis. The identification of the ZZS complex improves our understanding of the various activities required for crossover implementation and is likely applicable to other organisms, including mammals.

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Section: The Zzs Complex Shepherds Joint Molecules Toward a Pro-co Statesupporting

confidence: 90%

A meiotic XPF–ERCC1-like complex recognizes joint molecule recombination intermediates to promote crossover formation

et al. 2018

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“…Meiosis I is a process that homologous chromosomes are segregated and joined as tetrads, producing two haploid cells. And meiosis II is the second meiotic division involving the separation of sister chromatids [1, 2]. Errors in these processes, including deficient structure of spindle and unbalanced allocation of chromosomes could lead to the generation of aneuploidy [3, 4].…”

Section: Introductionmentioning

confidence: 99%

HDAC8 functions in spindle assembly during mouse oocyte meiosis

Zhang

Jiang

et al. 2017

Oncotarget

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HDAC8 is a class I histone deacetylase that functions in a variety of biological processes through its non-histone substrates. However, its roles during oocyte meiosis remain elusive. Here, we document that HDAC8 localizes at spindle poles and positively participates in the regulation of microtubule organization and spindle assembly in mouse oocytes. Depletion of HDAC8 by siRNA-based gene silencing results in various spindle defects and chromosome misalignment during oocyte meiotic maturation, accompanied by impaired kinetochore-microtubule attachments. Consequently, a higher incidence of aneuploidy is generated in HDAC8-depleted MII eggs. In addition, inhibition of HDAC8 activity with its selective inhibitor PCI-34051 phenocopies the spindle/chromosome defects resulting from HDAC8 depletion by siRNA injection. Finally, we find that HDAC8 is required for the correct localization of ϕ-tubulin to spindle poles. Collectively, these data reveal that HDAC8 plays a significant role in regulating spindle assembly and thus ensuring the euploidy in mouse eggs.

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“…Interestingly, this prior study also provided evidence that Spo11 activity can confer on HO DSBs, in trans , an increased capacity to resolve as a crossover. Medhi et al (2016) also reported evidence in support of the idea that Spo11 increases the likelihood that an artificially-supplied meiotic DSB will repair via a “meiotic-like” crossover pathway. However, whether artificial DSBs utilize meiosis-specific crossover factors, such as MutSγ, when Spo11 is absent was not examined in prior studies.…”

Section: Discussionmentioning

confidence: 82%

“…The HO endonuclease was found to promote interhomolog crossover recombination in spo11 yeast meiosis at higher frequency than in mitotic cells ( Malkova et al 1996b ; Malkova et al 2000 ), consistent with the idea that Spo11 -independent features of the meiotic nucleus may allow DSBs to engage with chromosome pairing and/or recombination pathways that promote favorable outcomes for meiosis; an example of such a mechanism might be the interhomolog bias-promoting activity of meiosis-specific chromosome axis proteins like Red1 and Rec8 , and/or meiosis-specific recombinase machinery ( Schwacha and Kleckner 1997 ; Hong et al 2013 ). However, the presence of Spo11 has also been found to exert a positive effect on the capacity of artificially-supplied meiotic DSBs to repair as interhomolog crossovers ( Malkova et al 1996b ; Malkova et al 2000 ; Neale et al 2002 ; Medhi et al 2016 ). The extent to which Spo11 activity is uniquely engaged with and capable of driving meiotic chromosome pairing processes remains obscure.…”

Section: Discussionmentioning

confidence: 99%

“…However, it was also noted that Spo11 activity has a trans effect on HO DSB repair: The presence of Spo11 correlated with a shorter interhomolog conversion tract length and an even higher likelihood of crossing over relative to when Spo11 is absent ( Malkova et al 2000 ). Independent studies using VDE, a site-specific endonuclease, provide additional evidence that Spo11 can increase the likelihood of interhomolog repair ( Neale et al 2002 ), reduce gene conversion tract length in trans ( Neale et al 2002 ), as well as influence the repair factors utilized ( Medhi et al 2016 ). Furthermore, when assessed, prior studies found no evidence that an HO -mediated or VDE-mediated DSB promotes SC assembly in spo11 mutant meiocytes ( Malkova et al 2000 ; Neale et al 2002 ), although partial SC assembly may have been missed because of the small size of the chromosomes sustaining the DSB.…”

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confidence: 99%

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HO Endonuclease-Initiated Recombination in Yeast Meiosis Fails To Promote Homologous Centromere Pairing and Is Not Constrained To Utilize the Dmc1 Recombinase

Yisehak

MacQueen

2018

G3 Genes|Genomes|Genetics

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Crossover recombination during meiosis is accompanied by a dramatic chromosome reorganization. In Saccharomyces cerevisiae, the onset of meiotic recombination by the Spo11 transesterase leads to stable pairwise associations between previously unassociated homologous centromeres followed by the intimate alignment of homologous axes via synaptonemal complex (SC) assembly. However, the molecular relationship between recombination and global meiotic chromosome reorganization remains poorly understood. In budding yeast, one question is why SC assembly initiates earliest at centromere regions while the DNA double strand breaks (DSBs) that initiate recombination occur genome-wide. We targeted the site-specific HO endonuclease to various positions on S. cerevisiae’s longest chromosome in order to ask whether a meiotic DSB’s proximity to the centromere influences its capacity to promote homologous centromere pairing and SC assembly. We show that repair of an HO-mediated DSB does not promote homologous centromere pairing nor any extent of SC assembly in spo11 meiotic nuclei, regardless of its proximity to the centromere. DSBs induced en masse by phleomycin exposure likewise do not promote homologous centromere pairing nor robust SC assembly. Interestingly, in contrast to Spo11, HO-initiated interhomolog recombination is not affected by loss of the meiotic kinase, Mek1, and is not constrained to use the meiosis-specific Dmc1 recombinase. These results strengthen the previously proposed idea that (at least some) Spo11 DSBs may be specialized in activating mechanisms that both 1) reinforce homologous chromosome alignment via homologous centromere pairing and SC assembly, and 2) establish Dmc1 as the primary strand exchange enzyme.

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

Cited by 8 publications

References 129 publications

A meiotic XPF–ERCC1-like complex recognizes joint molecule recombination intermediates to promote crossover formation

A meiotic XPF–ERCC1-like complex recognizes joint molecule recombination intermediates to promote crossover formation

HDAC8 functions in spindle assembly during mouse oocyte meiosis

HO Endonuclease-Initiated Recombination in Yeast Meiosis Fails To Promote Homologous Centromere Pairing and Is Not Constrained To Utilize the Dmc1 Recombinase

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