SUMO is a pervasive regulator of meiosis

eLife ◽

10.7554/elife.57720 ◽

2021 ◽

Vol 10 ◽

Author(s):

Nikhil R Bhagwat ◽

Shannon N Owens ◽

Masaru Ito ◽

Jay V Boinapalli ◽

Philip Poa ◽

...

Keyword(s):

Meiotic Prophase ◽

Protein Modification ◽

Budding Yeast ◽

Meiotic Chromosome ◽

S Phase ◽

Chromosome Organization ◽

Crossing Over ◽

Chromosome Synapsis ◽

Point Analysis ◽

Consensus Motifs

Protein modification by SUMO helps orchestrate the elaborate events of meiosis to faithfully produce haploid gametes. To date, only a handful of meiotic SUMO targets have been identified. Here we delineate a multidimensional SUMO-modified meiotic proteome in budding yeast, identifying 2747 conjugation sites in 775 targets, and defining their relative levels and dynamics. Modified sites cluster in disordered regions and only a minority match consensus motifs. Target identities and modification dynamics imply that SUMOylation regulates all levels of chromosome organization and each step of meiotic prophase I. Execution-point analysis confirms these inferences, revealing functions for SUMO in S-phase, the initiation of recombination, chromosome synapsis and crossing over. K15-linked SUMO chains become prominent as chromosomes synapse and recombine, consistent with roles in these processes. SUMO also modifies ubiquitin, forming hybrid oligomers with potential to modulate ubiquitin signaling. We conclude that SUMO plays diverse and unanticipated roles in regulating meiotic chromosome metabolism.

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Delineation of the SUMO-Modified Proteome Reveals Regulatory Functions Throughout Meiosis

10.1101/828442 ◽

2019 ◽

Cited By ~ 3

Author(s):

Nikhil R Bhagwat ◽

Shannon Owens ◽

Masaru Ito ◽

Jay Boinapalli ◽

Philip Poa ◽

...

Keyword(s):

Homologous Recombination ◽

Protein Modification ◽

Meiotic Chromosome ◽

S Phase ◽

Chromosome Organization ◽

Crossing Over ◽

Chromosome Synapsis ◽

Point Analysis ◽

Consensus Motifs ◽

Regulatory Functions

Protein modification by SUMO helps orchestrate the elaborate events of meiosis to faithfully produce haploid gametes. To date, only a handful of meiotic SUMO targets have been identified. Here we delineate a multidimensional SUMO-modified meiotic proteome in budding yeast, identifying 2747 conjugation sites in 775 targets, and defining their relative levels and dynamics. Modified sites cluster in disordered regions and only a minority match consensus motifs. Target identities and modification dynamics imply that SUMOylation regulates all levels of chromosome organization and each step of homologous recombination. Execution-point analysis confirms these inferences, revealing functions for SUMO in S-phase, the initiation of recombination, chromosome synapsis and crossing over. K15-linked SUMO chains become prominent as chromosomes synapse and recombine, consistent with roles in these processes. SUMO also modifies ubiquitin, forming hybrid oligomers with potential to modulate ubiquitin signaling. We conclude that SUMO plays diverse and unanticipated roles in regulating meiotic chromosome metabolism.

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The Budding Yeast Msh4 Protein Functions in Chromosome Synapsis and the Regulation of Crossover Distribution

Genetics ◽

10.1093/genetics/158.3.1013 ◽

2001 ◽

Vol 158 (3) ◽

pp. 1013-1025 ◽

Cited By ~ 7

Author(s):

Janet E Novak ◽

Petra B Ross-Macdonald ◽

G Shirleen Roeder

Keyword(s):

Mismatch Repair ◽

Budding Yeast ◽

Null Mutation ◽

Crossing Over ◽

Wild Type ◽

Crossover Interference ◽

Meiotic Chromosomes ◽

Chromosome Synapsis ◽

Protein Functions ◽

Or Gene

AbstractThe budding yeast MSH4 gene encodes a MutS homolog produced specifically in meiotic cells. Msh4 is not required for meiotic mismatch repair or gene conversion, but it is required for wild-type levels of crossing over. Here, we show that a msh4 null mutation substantially decreases crossover interference. With respect to the defect in interference and the level of crossing over, msh4 is similar to the zip1 mutant, which lacks a structural component of the synaptonemal complex (SC). Furthermore, epistasis tests indicate that msh4 and zip1 affect the same subset of meiotic crossovers. In the msh4 mutant, SC formation is delayed compared to wild type, and full synapsis is achieved in only about half of all nuclei. The simultaneous defects in synapsis and interference observed in msh4 (and also zip1 and ndj1/tam1) suggest a role for the SC in mediating interference. The Msh4 protein localizes to discrete foci on meiotic chromosomes and colocalizes with Zip2, a protein involved in the initiation of chromosome synapsis. Both Zip2 and Zip1 are required for the normal localization of Msh4 to chromosomes, raising the possibility that the zip1 and zip2 defects in crossing over are indirect, resulting from the failure to localize Msh4 properly.

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A conserved filamentous assembly underlies the structure of the meiotic chromosome axis

eLife ◽

10.7554/elife.40372 ◽

2019 ◽

Vol 8 ◽

Cited By ~ 26

Author(s):

Alan MV West ◽

Scott C Rosenberg ◽

Sarah N Ur ◽

Madison K Lehmer ◽

Qiaozhen Ye ◽

...

Keyword(s):

Meiotic Recombination ◽

Budding Yeast ◽

Meiotic Chromosome ◽

Coiled Coil ◽

Chromosome Organization ◽

Molecular Architecture ◽

Master Regulators ◽

Core Proteins ◽

Protein Components ◽

Chromosome Axis

The meiotic chromosome axis plays key roles in meiotic chromosome organization and recombination, yet the underlying protein components of this structure are highly diverged. Here, we show that ‘axis core proteins’ from budding yeast (Red1), mammals (SYCP2/SYCP3), and plants (ASY3/ASY4) are evolutionarily related and play equivalent roles in chromosome axis assembly. We first identify ‘closure motifs’ in each complex that recruit meiotic HORMADs, the master regulators of meiotic recombination. We next find that axis core proteins form homotetrameric (Red1) or heterotetrameric (SYCP2:SYCP3 and ASY3:ASY4) coiled-coil assemblies that further oligomerize into micron-length filaments. Thus, the meiotic chromosome axis core in fungi, mammals, and plants shares a common molecular architecture, and likely also plays conserved roles in meiotic chromosome axis assembly and recombination control.

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Crossing over is coupled to late meiotic prophase bivalent differentiation through asymmetric disassembly of the SC

The Journal of Cell Biology ◽

10.1083/jcb.200410144 ◽

2005 ◽

Vol 168 (5) ◽

pp. 683-689 ◽

Cited By ~ 84

Author(s):

Kentaro Nabeshima ◽

Anne M. Villeneuve ◽

Monica P. Colaiácovo

Keyword(s):

Caenorhabditis Elegans ◽

Symmetry Breaking ◽

Synaptonemal Complex ◽

Central Region ◽

Meiotic Prophase ◽

Homologous Chromosome ◽

Meiotic Chromosome ◽

Crossing Over ◽

Γ Irradiation ◽

Irradiation Treatment

Homologous chromosome pairs (bivalents) undergo restructuring during meiotic prophase to convert a configuration that promotes crossover recombination into one that promotes bipolar spindle attachment and localized cohesion loss. We have imaged remodeling of meiotic chromosome structures after pachytene exit in Caenorhabditis elegans. Chromosome shortening during diplonema is accompanied by coiling of chromosome axes and highly asymmetric departure of synaptonemal complex (SC) central region proteins SYP-1 and SYP-2, which diminish over most of the length of each desynapsing bivalent while becoming concentrated on axis segments distal to the single emerging chiasma. This and other manifestations of asymmetry along chromosomes are lost in synapsis-proficient crossover-defective mutants, which often retain SYP-1,2 along the full lengths of coiled diplotene axes. Moreover, a γ-irradiation treatment that restores crossovers in the spo-11 mutant also restores asymmetry of SYP-1 localization. We propose that crossovers or crossover precursors serve as symmetry-breaking events that promote differentiation of subregions of the bivalent by triggering asymmetric disassembly of the SC.

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Initiation of meiotic chromosome synapsis at centromeres in budding yeast

Genes & Development ◽

10.1101/gad.1709408 ◽

2008 ◽

Vol 22 (22) ◽

pp. 3217-3226 ◽

Cited By ~ 72

Author(s):

T. Tsubouchi ◽

A. J. MacQueen ◽

G. S. Roeder

Keyword(s):

Budding Yeast ◽

Meiotic Chromosome ◽

Chromosome Synapsis

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Topoisomerases Modulate the Timing of Meiotic DNA Breakage and Chromosome Morphogenesis in Saccharomyces cerevisiae

Genetics ◽

10.1534/genetics.120.303060 ◽

2020 ◽

Vol 215 (1) ◽

pp. 59-73 ◽

Cited By ~ 3

Author(s):

Jonna Heldrich ◽

Xiaoji Sun ◽

Luis A. Vale-Silva ◽

Tovah E. Markowitz ◽

Andreas Hochwagen

Keyword(s):

Saccharomyces Cerevisiae ◽

Meiotic Prophase ◽

Meiotic Chromosome ◽

Strand Break ◽

Temperature Sensitive ◽

Chromosomal Dna ◽

Link Type ◽

Chromosome Synapsis ◽

Intergenic Regions

During meiotic prophase, concurrent transcription, recombination, and chromosome synapsis place substantial topological strain on chromosomal DNA, but the role of topoisomerases in this context remains poorly defined. Here, we analyzed the roles of topoisomerases I and II (Top1 and Top2) during meiotic prophase in Saccharomyces cerevisiae. We show that both topoisomerases accumulate primarily in promoter-containing intergenic regions of actively transcribing genes, including many meiotic double-strand break (DSB) hotspots. Despite the comparable binding patterns, top1 and top2 mutations have different effects on meiotic recombination. TOP1 disruption delays DSB induction and shortens the window of DSB accumulation by an unknown mechanism. By contrast, temperature-sensitive top2-1 mutants exhibit a marked delay in meiotic chromosome remodeling and elevated DSB signals on synapsed chromosomes. The problems in chromosome remodeling were linked to altered Top2 binding patterns rather than a loss of Top2 catalytic activity, and stemmed from a defect in recruiting the chromosome remodeler Pch2/TRIP13 to synapsed chromosomes. No chromosomal defects were observed in the absence of TOP1. Our results imply independent roles for Top1 and Top2 in modulating meiotic chromosome structure and recombination.

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Topoisomerases modulate the timing of meiotic DNA breakage and chromosome morphogenesis in Saccharomyces cerevisiae

10.1101/672337 ◽

2019 ◽

Cited By ~ 1

Author(s):

Jonna Heldrich ◽

Xiaoji Sun ◽

Luis A. Vale-Silva ◽

Tovah E. Markowitz ◽

Andreas Hochwagen

Keyword(s):

Saccharomyces Cerevisiae ◽

Meiotic Recombination ◽

Meiotic Prophase ◽

Meiotic Chromosome ◽

Strand Break ◽

Temperature Sensitive ◽

Chromosomal Dna ◽

Meiotic Chromosomes ◽

Chromosome Synapsis ◽

Intergenic Regions

AbstractDuring meiotic prophase, concurrent transcription, recombination, and chromosome synapsis, place substantial topological strain on chromosomal DNA, but the role of topoisomerases in this context remains poorly defined. Here, we analyzed the roles topoisomerases I and II (Top1 and Top2) during meiotic prophase in Saccharomyces cerevisiae. We show that both topoisomerases accumulate primarily in promoter-containing intergenic regions of actively transcribing genes. Enrichment partially overlaps meiotic double-strand break (DSB) hotspots, but disruption of either topoisomerase has different effects during meiotic recombination. TOP1 disruption delays DSB induction and shortens the window of DSB accumulation by an unknown mechanism. By contrast, temperature-sensitive top2-1 mutants accumulate DSBs on synapsed chromosomes and exhibit a marked delay in meiotic chromosome remodeling. This defect results from a delay in recruiting the meiotic chromosome remodeler Pch2/TRIP13 but, unexpectedly, is not due to a loss of Top2 catalytic activity. Instead, mutant Top2-1 protein has reduced contact with chromatin but remains associated with meiotic chromosomes, and we provide evidence that this altered binding is responsible for the delay in chromosome remodeling. Our results imply independent roles for topoisomerases I and II in modulating meiotic recombination.

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The rec102 mutant of yeast is defective in meiotic recombination and chromosome synapsis.

Genetics ◽

10.1093/genetics/130.1.59 ◽

1992 ◽

Vol 130 (1) ◽

pp. 59-69

Author(s):

J Bhargava ◽

J Engebrecht ◽

G S Roeder

Keyword(s):

Synaptonemal Complex ◽

Chromosome Segregation ◽

Meiotic Recombination ◽

Meiotic Chromosome ◽

Crossing Over ◽

Homologous Chromosomes ◽

Chromosome Synapsis ◽

Recombination Pathway ◽

Yeast Mutants ◽

Meiosis I

Abstract A mutation at the REC102 locus was identified in a screen for yeast mutants that produce inviable spores. rec102 spore lethality is rescued by a spo13 mutation, which causes cells to bypass the meiosis I division. The rec102 mutation completely eliminates meiotically induced gene conversion and crossing over but has no effect on mitotic recombination frequencies. Cytological studies indicate that the rec102 mutant makes axial elements (precursors to the synaptonemal complex), but homologous chromosomes fail to synapse. In addition, meiotic chromosome segregation is significantly delayed in rec102 strains. Studies of double and triple mutants indicate that the REC102 protein acts before the RAD52 gene product in the meiotic recombination pathway. The REC102 gene was cloned based on complementation of the mutant defect and the gene was mapped to chromosome XII between CDC25 and STE11.

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Meiosis in asynaptic yeast.

Genetics ◽

10.1093/genetics/126.3.563 ◽

1990 ◽

Vol 126 (3) ◽

pp. 563-574 ◽

Cited By ~ 7

Author(s):

B Rockmill ◽

G S Roeder

Keyword(s):

Saccharomyces Cerevisiae ◽

Synaptonemal Complex ◽

Gene Conversion ◽

Gene Product ◽

Meiotic Prophase ◽

Crossing Over ◽

Intrachromosomal Recombination ◽

Reciprocal Exchange ◽

Chromosome Synapsis ◽

Moderate Reduction

Abstract The Saccharomyces cerevisiae red1 mutant fails to assemble synaptonemal complex during meiotic prophase. This mutant displays locus-specific reductions in interchromosomal gene conversion and a moderate reduction in crossing over. The occurrence of a significant amount of meiotically induced recombination in the red1 mutant indicates that the synaptonemal complex is not absolutely required for meiotic exchange. The RED1 gene product is required for intrachromosomal recombination in some assays but not others. Chromosomes that have undergone reciprocal exchange nevertheless nondisjoin in red1 mutants, indicating that crossovers are not sufficient for disjunction. Epistasis studies reveal that HOP1 is epistatic to RED1, and that RED1 acts in an independent pathway from MER1. A model for the function of the RED1 gene product in chromosome synapsis is discussed.

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