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

2019 ◽  
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.

scholarly journals SUMO is a pervasive regulator of meiosis

eLife ◽  
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.

scholarly journals The crossover function of MutSγ is activated via Cdc7-dependent stabilization of Msh4

2018 ◽  
Author(s):  
Wei He ◽  
H.B.D. Prasada Rao ◽  
Shangming Tang ◽  
Nikhil Bhagwat ◽  
Dhananjaya S. Kulkarni ◽  
...  
Keyword(s):  
Homologous Recombination ◽  
Chromosome Segregation ◽  
Holliday Junctions ◽  
Strand Exchange ◽  
Crossing Over ◽  
Chromosome Synapsis ◽  
Meiotic Crossover ◽  
Dna Strand Exchange ◽  
Dna Strand ◽  
Fundamental Mechanism

SUMMARYThe MutSγ complex, Msh4-Msh5, binds DNA joint-molecule (JM) intermediates during homologous recombination to promote crossing over and accurate chromosome segregation at the first division of meiosis. MutSγ facilitates the formation and biased resolution of crossover-specific JM intermediates called double Holliday junctions. Here we show that these activities are governed by regulated proteasomal degradation. MutSγ is initially inactive for crossing over due to an N-terminal degron on Msh4 that renders it unstable. Activation of MutSγ requires the Dbf4-dependent kinase, Cdc7 (DDK), which directly phosphorylates and thereby neutralizes the Msh4 degron. Phosphorylated Msh4 is chromatin bound and requires DNA strand exchange and chromosome synapsis, implying that DDK specifically targets MutSγ that has already bound nascent JMs. Our study establishes regulated protein degradation as a fundamental mechanism underlying meiotic crossover control.

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

Genetics ◽  
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.

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

Genetics ◽  
2001 ◽  
Vol 158 (3) ◽  
pp. 1013-1025 ◽  
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.

ATM and RPA in meiotic chromosome synapsis and recombination

1997 ◽  
Vol 17 (4) ◽  
pp. 457-461 ◽  
Author(s):  
Annemieke W. Plug ◽  
Antoine H.F.M Peters ◽  
Yang Xu ◽  
Kathleen S. Keegan ◽  
Merl F. Hoekstra ◽  
...  
Keyword(s):  
Meiotic Chromosome ◽  
Chromosome Synapsis

Concluding remarks

1977 ◽  
Vol 277 (955) ◽  
pp. 371-376 ◽  
Keyword(s):  
Genetic Recombination ◽  
Meiotic Behaviour ◽  
Chromosome Organization ◽  
Base Sequence ◽  
Crossing Over ◽  
Primary Target ◽  
Sequence Complexity ◽  
A Genome ◽  
Chromosome Alignment ◽  
Single Pattern

Professor Darlington opened the meeting by challenging us with the view that chromosomes made the laws of heredity, rather than heredity fashioning the organization of chromosomes. To keep this wheel of logic spinning, it may be said that chromosomes also made the process of meiosis and thus determined the laws of meiotic exchange. I choose this gambit because our discussions lent considerable emphasis to the view that chromosome complexity compels its own sets of distinctive, and perhaps varied, mechanisms to effect the ultimate event of molecular recombination. The complexity that leads molecular recombination to operate in elaborate meiotic moulds is not, it should be emphasized, base sequence complexity. On the contrary, sequence repeats and genetic homoeologies, though adding disproportionately little to the base sequence complexity of a genome, adds considerably to the complexity of effecting chromosome alignment and crossing over. How chromosomes of diverse genetic content manage that complexity and in the process mould the characteristics of meiotic behaviour has been the primary target of our deliberations. That no single pattern of meiotic conduct was perceived in consequence of the discussions, is to be expected. To the extent that genomes differ in various aspects of chromosome organization - and that they do is patent - the particulars of meiotic organization might also differ. Although a strong sentiment was occasionally expressed for a single universal process of meiosis, it is my opinion that sameness and universality may be mistakenly treated as synonyms. Universals provide for diversity; they do not impose sameness. The task of identifying universal threads among different meiotic fabrics is not a straightforward one. The ultimate act of genetic recombination offers no detailed guide to the routes by which it may be achieved. Indeed, it is the structure of the chromosome that dictates the route ; recombination only signals the direction.

scholarly journals X Chromosome Control of Meiotic Chromosome Synapsis in Mouse Inter-Subspecific Hybrids

PLoS Genetics ◽  
2014 ◽  
Vol 10 (2) ◽  
pp. e1004088 ◽  
Author(s):  
Tanmoy Bhattacharyya ◽  
Radka Reifova ◽  
Sona Gregorova ◽  
Petr Simecek ◽  
Vaclav Gergelits ◽  
...  
Keyword(s):  
X Chromosome ◽  
Meiotic Chromosome ◽  
Chromosome Synapsis

scholarly journals The M26 Hotspot of Schizosaccharomyces pombe Stimulates Meiotic Ectopic Recombination and Chromosomal Rearrangements

Genetics ◽  
1998 ◽  
Vol 149 (3) ◽  
pp. 1191-1204 ◽  
Author(s):  
Jeffrey B Virgin ◽  
Jeffrey P Bailey
Keyword(s):  
Homologous Recombination ◽  
Schizosaccharomyces Pombe ◽  
Dna Sequences ◽  
Chromosomal Rearrangements ◽  
Low Frequency ◽  
Repeated Sequences ◽  
Crossing Over ◽  
Ectopic Recombination ◽  
Recombination Hotspots ◽  
Integration Sites

Abstract Homologous recombination is increased during meiosis between DNA sequences at the same chromosomal position (allelic recombination) and at different chromosomal positions (ectopic recombination). Recombination hotspots are important elements in controlling meiotic allelic recombination. We have used artificially dispersed copies of the ade6 gene in Schizosaccharomyces pombe to study hotspot activity in meiotic ectopic recombination. Ectopic recombination was reduced 10–1000-fold relative to allelic recombination, and was similar to the low frequency of ectopic recombination between naturally repeated sequences in S. pombe. The M26 hotspot was active in ectopic recombination in some, but not all, integration sites, with the same pattern of activity and inactivity in ectopic and allelic recombination. Crossing over in ectopic recombination, resulting in chromosomal rearrangements, was associated with 35–60% of recombination events and was stimulated 12-fold by M26. These results suggest overlap in the mechanisms of ectopic and allelic recombination and indicate that hotspots can stimulate chromosomal rearrangements.

scholarly journals Shu Proteins Promote the Formation of Homologous Recombination Intermediates That Are Processed by Sgs1-Rmi1-Top3

2007 ◽  
Vol 18 (10) ◽  
pp. 4062-4073 ◽  
Author(s):  
Hocine W. Mankouri ◽  
Hien-Ping Ngo ◽  
Ian D. Hickson
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Homologous Recombination ◽  
S Phase ◽  
Specific Role ◽  
Homologous Recombination Repair ◽  
Recombination Repair ◽  
Mutant Phenotypes ◽  
Precise Role

CSM2, PSY3, SHU1, and SHU2 (collectively referred to as the SHU genes) were identified in Saccharomyces cerevisiae as four genes in the same epistasis group that suppress various sgs1 and top3 mutant phenotypes when mutated. Although the SHU genes have been implicated in homologous recombination repair (HRR), their precise role(s) within this pathway remains poorly understood. Here, we have identified a specific role for the Shu proteins in a Rad51/Rad54-dependent HRR pathway(s) to repair MMS-induced lesions during S-phase. We show that, although mutation of RAD51 or RAD54 prevented the formation of MMS-induced HRR intermediates (X-molecules) arising during replication in sgs1 cells, mutation of SHU genes attenuated the level of these structures. Similar findings were also observed in shu1 cells in which Rmi1 or Top3 function was impaired. We propose a model in which the Shu proteins act in HRR to promote the formation of HRR intermediates that are processed by the Sgs1-Rmi1-Top3 complex.

scholarly journals The Arabidopsis HOP2 Gene Has a Role in Preventing illegitimate Exchanges between Nonhomologous Chromosomes

2021 ◽  
Author(s):  
YIsell Farahani-Tafreshi ◽  
Chun Wei ◽  
Peilu Gan ◽  
Jenya Daradur ◽  
C. Daniel Riggs ◽  
...  
Keyword(s):  
Active Role ◽  
Crossing Over ◽  
Wild Type ◽  
Positive Role ◽  
Homologous Chromosomes ◽  
Chromosome Synapsis ◽  
Radiation Induced ◽  
Nonhomologous Chromosome ◽  
Chromosome Exchanges

Meiotic homologous chromosomes pair up and undergo crossing over. In many eukaryotes both intimate pairing and crossing over require the induction of double stranded breaks (DSBs) and subsequent repair via Homologous Recombination (HR). In these organisms, two key proteins are the recombinases RAD51 and DMC1. Recombinase-modulators HOP2 and MND1 have been identified as proteins that assist RAD51 and DMC1 and are needed to promote stabilized pairing. We have probed the nature of the genetic lesions seen in hop2 mutants and looked at the role of HOP2 in the fidelity of genetic exchanges. Using γH2AX as a marker for unrepaired DSBs we found that hop2-1 and mnd1 mutants have different appearance/disappearance for DSBs than wild type, but all DSBs are repaired by mid-late pachytene. Therefore, the bridges and fragments seen from metaphase I onward are due to mis-repaired DSBs, not unrepaired ones. Studying Arabidopsis haploid meiocytes we found that wild type haploids produced the expected five univalents, but hop2-1 haploids suffered many illegitimate exchanges that were stable enough to produce bridged chromosomes during segregation. Our results suggest that HOP2 has a significant active role in preventing nonhomologous associations. We also found evidence that HOP2 plays a role in preventing illegitimate exchanges during repair of radiation-induced DSBs in rapidly dividing petal cells. Thus, HOP2 plays both a positive role in promoting homologous chromosome synapsis and a separable role in preventing nonhomologous chromosome exchanges. Possible mechanisms for this second important role are discussed.

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