Persistent DNA-break potential near telomeres increases initiation of meiotic recombination on short chromosomes

Subramanian, Vijayalakshmi V.; Zhu, Xuan; Markowitz, Tovah E.; Silva, Luis Andre Vale; San-Segundo, Pedro A.; Hollingsworth, Nancy M.; Keeney, Scott; Hochwagen, Andreas

doi:10.1101/201889

Cited by 5 publications

(3 citation statements)

References 101 publications

(167 reference statements)

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“…Alternatively, Nup2/Nup60 might be acting through Hop1 or Pch1. Nup2 facilitates removal of Hop1 from interstitial regions of chromosomes, allowing double strand break potential to persist near the chromosome ends and helping to ensure that short chromosomes form a crossover (Subramanian et al 2019). Nup2 has also been shown to promote association of the checkpoint protein Pch2 with meiotic chromosomes and to control the distribution of Pch2 between the nucleus and the cytoplasm (Herruzo et al 2021).…”

Section: Discussionmentioning

confidence: 99%

The Nup2 meiotic-autonomous region relieves autoinhibition of Nup60 to promote progression of meiosis and sporulation in Saccharomyces cerevisiae

Komachi

Burgess

2021

Preprint

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During meiosis, chromosomes undergo dramatic changes in structural organization, nuclear positioning, and motion. Although the nuclear pore complex has been shown to affect genome organization and function in vegetative cells, its role in meiotic chromosome dynamics has remained largely unexplored. Recent work in the budding yeast Saccharomyces cerevisiae demonstrated that the mobile nucleoporin Nup2 is required for normal progression through meiosis I prophase and sporulation in strains where telomere-led chromosome movement has been compromised. The meiotic autonomous region (MAR), a short fragment of Nup2 responsible for its role in meiosis, was shown to localize to the nuclear envelope via Nup60 and to bind to meiotic chromosomes. To understand the relative contribution these two activities have on MAR function, we first carried out a screen for MAR mutants defective in sporulation and found that all the mutations disrupt interaction with both Nup60 and meiotic chromosomes. Moreover, nup60 mutants phenocopy nup2 mutants, exhibiting similar nuclear division kinetics, sporulation efficiencies, and genetic interactions with mutations that affect the telomere bouquet. Although full-length Nup60 requires Nup2 for function, removal of Nup60s C-terminus allows Nup60 to bind meiotic chromosomes and promote sporulation without Nup2. In contrast, binding of the MAR to meiotic chromosomes is completely dependent on Nup60. Our findings uncover an inhibitory function for the Nup60 C-terminus and suggest that Nup60 mediates recruitment of meiotic chromosomes to the nuclear envelope, while Nup2 plays a secondary role counteracting Nup60s autoinhibition.

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Section: Discussionmentioning

confidence: 99%

The Nup2 meiotic-autonomous region relieves autoinhibition of Nup60 to promote progression of meiosis and sporulation in Saccharomyces cerevisiae

Komachi

Burgess

2021

Preprint

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“…At least in S. cerevisiae, higher order chromosome architecture also influences recombination potential, with some chromosomes (mostly shorter chromosomes) experiencing earlier and more substantial DSB activity than larger chromosomes (Pan et al, 2011;Murakami et al, 2018). Subtelomeric regions also experience elevated DSB frequency (Subramanian et al, 2019), consistent with reduced levels of compaction compared to interstitial regions within the chromosome arm (Schalbetter et al, 2017). Recombination frequency is further influenced by DSBdependent negative regulation; a process that appears conserved across all eukaryotes examined so far (Joyce et al, 2011;Lange et al, 2011;Carballo et al, 2013;Garcia et al, 2015;Mohibullah & Keeney, 2017).…”

Section: (B) Timing and Frequencymentioning

confidence: 99%

Meiosis and beyond – understanding the mechanistic and evolutionary processes shaping the germline genome

et al. 2021

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The separation of germ cell populations from the soma is part of the evolutionary transition to multicellularity. Only genetic information present in the germ cells will be inherited by future generations, and any molecular processes affecting the germline genome are therefore likely to be passed on. Despite its prevalence across taxonomic kingdoms, we are only starting to understand details of the underlying micro-evolutionary processes occurring at the germline genome level. These include segregation, recombination, mutation and selection and can occur at any stage during germline differentiation and mitotic germline proliferation to meiosis and post-meiotic gamete maturation. Selection acting on germ cells at any stage from the diploid germ cell to the haploid gametes may cause significant deviations from Mendelian inheritance and may be more widespread than previously assumed. The mechanisms that affect and potentially alter the genomic sequence and allele frequencies in the germline are pivotal to our understanding of heritability. With the rise of new sequencing technologies, we are now able to address some of these unanswered questions. In this review, we comment on the most recent developments in this field and identify current gaps in our knowledge.

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“…The non-uniform distribution of Hop1 is maintained by Pch2, a hexameric AAA+ ATPase (CHEN et al 2014). In pch2 mutants, Hop1 persists longer and is more uniformly distributed on chromosomes; this is accompanied by a delay in meiotic progression and changes in the distribution of late-forming DSBs and COs (BÖRNER et al 2008;JOSHI et al 2009;ZANDERS AND ALANI 2009;LAMBING et al 2015;SUBRAMANIAN et al 2016;SUBRAMANIAN et al 2018).…”

Section: Introductionmentioning

confidence: 99%

Noncanonical contributions of MutLγ to VDE-initiated crossovers duringSaccharomyces cerevisiaemeiosis

Shodhan

Medhi

Lichten

2019

Preprint

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In Saccharomyces cerevisiae, the meiosis-specific axis proteins Hop1 and Red1 are present nonuniformly across the genome. In a previous study, the meiosis-specific VMA1-derived endonuclease (VDE) was used to examine Spo11-independent recombination in a recombination reporter inserted in a Hop1/Red1-enriched region (HIS4) and in a Hop1/Red1-poor region (URA3). VDE-initiated crossovers at HIS4 were mostly dependent on Mlh3, a component of the MutLg meiotic recombination intermediate resolvase, while VDE-initiated crossovers at URA3 were mostly Mlh3-independent. These differences were abolished in the absence of the chromosome axis remodeler Pch2, and crossovers at both loci become partly Mlh3-dependent. To test the generality of these observations, we examined inserts at six additional loci that differed in terms of Hop1/Red1 enrichment, chromosome size, and distance from centromeres and telomeres. All six loci behaved similarly to URA3: the vast majority of VDE-initiated crossovers were Mlh3-independent. This indicates that, counter to previous suggestions, meiotic chromosome axis protein enrichment is not a primary determinant of which recombination pathway gives rise to crossovers during VDE-initiated meiotic recombination. In pch2∆ mutants, the fraction of VDE-induced crossovers that were Mlh3dependent increased to levels previously observed for Spo11-initiated crossovers in pch2∆, indicating that Pch2-dependent processes play an important role in controlling the distribution of factors necessary for MutLg-dependent crossovers.

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Persistent DNA-break potential near telomeres increases initiation of meiotic recombination on short chromosomes

Cited by 5 publications

References 101 publications

The Nup2 meiotic-autonomous region relieves autoinhibition of Nup60 to promote progression of meiosis and sporulation in Saccharomyces cerevisiae

The Nup2 meiotic-autonomous region relieves autoinhibition of Nup60 to promote progression of meiosis and sporulation in Saccharomyces cerevisiae

Meiosis and beyond – understanding the mechanistic and evolutionary processes shaping the germline genome

Noncanonical contributions of MutLγ to VDE-initiated crossovers duringSaccharomyces cerevisiaemeiosis

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