Separable Roles for a Caenorhabditis elegans RMI1 Homolog in Promoting and Antagonizing Meiotic Crossovers Ensure Faithful Chromosome Inheritance

Jagut, Marlène; Hamminger, Patricia; Woglar, Alexander; Millonigg, Sophia; Paulin, Luis F; Mikl, Martin; Stritto, Maria Rosaria Dello; Tang, Lois; Habacher, Cornelia; Tam, Angela; Gallach, Miguel; Haeseler, Arndt von; Villeneuve, Anne M.; Jantsch, Verena

doi:10.1371/journal.pbio.1002412

Cited by 32 publications

(87 citation statements)

References 80 publications

(90 reference statements)

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“…Unexpectedly, these studies revealed that Rmi1 and Top3 act independently of Sgs1 to disentangle chromosomes in late meiotic prophase, allowing for proper chromosomal segregation [12,40]. Similar BLM-independent roles for RMI1 and TOP3α have been described in Arabidopsis [20, 41–43] and C. elegans [44], but it is likely that functions described below for BLM orthologs also require these interacting proteins.…”

Section: S Cerevisiae Sgs1: the Pioneering Meiotic Pathway Regulatormentioning

confidence: 86%

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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Section: S Cerevisiae Sgs1: the Pioneering Meiotic Pathway Regulatormentioning

confidence: 86%

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

Hatkevich

Sekelsky

2017

BioEssays

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“…The localization of Zip3 orthologs is consistent with their involvement in the transformation of early recombination intermediates into crossovers (Box1). All members of the family exhibit a broad pattern of colocalization with the SC early in prophase, followed by a restriction to a smaller subset of foci which overlap with cytological CO markers (MutSg, MutLg, or recombination nodules, SC structures which correlate with crossing over [30]) [16,18,20,22,24,28,[31][32][33][34]. Consequently, the collective analyses indicate that SUMO and/or ubiquitin E3 ligase-like proteins localize to the SC and to CO sites to mediate the formation of crossovers.…”

Section: Conserved Roles For the Zip3 Family During Meiotic Prophasementioning

confidence: 94%

“…All members of the family exhibit a broad pattern of colocalization with the SC early in prophase, followed by a restriction to a smaller subset of foci which overlap with cytological CO markers (MutSg, MutLg, or recombination nodules, SC structures which correlate with crossing over [30]) [16,18,20,22,24,28,[31][32][33][34]. All members of the family exhibit a broad pattern of colocalization with the SC early in prophase, followed by a restriction to a smaller subset of foci which overlap with cytological CO markers (MutSg, MutLg, or recombination nodules, SC structures which correlate with crossing over [30]) [16,18,20,22,24,28,[31][32][33][34].…”

Section: Conserved Roles For the Zip3 Family During Meiotic Prophasementioning

confidence: 99%

“…All studied Zip3 orthologs follow a general pattern of appearance, characterized by initial localization to the SC in the form of discrete puncta, linear coterminous tracks, or both. With meiotic progression, the Zip3 orthologs undergo a dynamic restriction to a smaller number of distinct foci, accompanied by increasing overlap with CO markers [16,18,20,22,24,28,[31][32][33][34]. Some unique aspects of individual Zip3 ortholog localization, such as the perinuclear and SPB localization of Hei10 in S. macrospora [24], can also be inferred to be functionally consequential.…”

Section: Conservation Of Zip3 Family Protein Localization and Functionmentioning

confidence: 99%

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The proteasome enters the meiotic prophase fray

Vujin

2017

BioEssays

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The segregation of homologous chromosomes in meiosis depends on their ability to locate one another in the nucleus and establish a physical association through crossing over. A tightly regulated number of crossovers (COs) emerges following repair of induced DNA double-strand breaks by homologous recombination (HR), but the process of how HR intermediates transition into COs is still poorly understood. Two recent studies by Ahuja et al. and Rao et al. have revealed a role for chromosomally localized proteasomes in choreographing both homologous chromosome pairing and the evolution of HR intermediates into segregation-competent COs. Using chemical inhibition of the proteasome and mutant analysis, the collective data reveal conserved functions for both the proteasome and a family of E3 ligases that can direct or compete with its activity in ensuring CO formation. Here, we review these findings and the impact of the discovery that protein modification dynamics and proteasomal activity cooperate to regulate key meiotic processes.Abbreviations: CO, cross-over; CP, core particle (of the proteasome); DSB, double-strand break; HR, homologous recombination; RP, regulatory particle (of the proteasome); SC, synaptonemal complex; SEI, single-end invasion; SUMO, small ubiquitin-like modifier; Ub, ubiquitin.

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“…Alteration in crossover distribution in the brc-1 mutant may result from changes in the chromatin landscape, which has been linked to BRCA1 function in mammals (BROERING et al 2014;DENSHAM et al 2016), and has been shown to alter crossover patterning (MEZARD et al 2015;YU et al 2016). A surprising number of C. elegans meiotic mutants display altered crossover distribution (ZETKA AND ROSE 1995;MENEELY et al 2012;SAITO et al 2012;SAITO et al 2013;WAGNER et al 2010;CHUNG et al 2015;HONG et al 2016;JAGUT et al 2016;Janisiw et al 2020). While the underlying mechanisms are not clear, it may be a consequence of altering the use of crossover versus non-crossover pathways within a particular chromatin environment as suggested by Saito and Colaiacovo (SAITO AND COLAIACOVO 2017).…”

Section: Brc-1-brd-1 Function When Male Meiosis Is Perturbedmentioning

confidence: 99%

C. elegans BRC-1-BRD-1 functions at an early step of DSB processing and inhibits supernumerary crossovers during male meiosis

Engebrecht

Li²,

Hariri³

2020

Preprint

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Meiosis is regulated in a sex-specific manner to produce two distinct gametes, sperm and oocytes, for sexual reproduction. To determine how meiotic recombination is regulated in spermatogenesis, we analyzed the meiotic phenotypes of mutants in the tumor suppressor E3 ubiquitin ligase BRC-1-BRD-1 complex in Caenorhabditis elegans male meiosis. Unlike in mammals, this complex is not required for meiotic sex chromosome inactivation, the process whereby hemizygous sex chromosomes are transcriptionally silenced. Interestingly, brc-1 and brd-1 mutants showed meiotic recombination phenotypes that are largely opposing to those previously reported for female meiosis.Fewer meiotic recombination foci marked by the recombinase RAD-51 were observed in brc-1 and brd-1 mutants, and the reduction in RAD-51 foci can be suppressed by mutation of nonhomologous end joining proteins. We show that concentration of BRC-1-BRD-1 to sites of meiotic recombination is dependent on DNA end resection, suggesting that BRC-1-BRD-1 regulates the processing of meiotic double strand breaks to promote repair by homologous recombination, similar to a role for the complex in somatic cells. We also show that BRC-1-BRD-1 is important to promote progeny viability when male meiosis is perturbed by mutations that block the pairing and synapsis of different chromosome pairs, although the complex is not required to stabilize the RAD-51 filament as in female meiosis under the same conditions. Analyses of crossover designation and formation reveal that BRC-1-BRD-1 inhibits supernumerary crossovers when meiosis is perturbed. Together, our findings suggest that BRC-1-BRD-1 regulates different aspects of meiotic recombination in male and female meiosis.

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Separable Roles for a Caenorhabditis elegans RMI1 Homolog in Promoting and Antagonizing Meiotic Crossovers Ensure Faithful Chromosome Inheritance

Cited by 32 publications

References 80 publications

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

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

The proteasome enters the meiotic prophase fray

C. elegans BRC-1-BRD-1 functions at an early step of DSB processing and inhibits supernumerary crossovers during male meiosis

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