The role of OsCOM1 in homologous chromosome synapsis and recombination in rice meiosis

Abstract Deletion of Hop2 in mice eliminates homologous chromosome synapsis and disrupts double-strand break (DSB) repair through homologous recombination. HOP2 in vitro shows two distinctive activities: when it is incorporated into a HOP2–MND1 complex it stimulates DMC1 and RAD51 recombination activities and the purified HOP2 alone is proficient in promoting strand invasion. We observed that a fraction of Mnd1−/− spermatocytes, which express HOP2 but apparently have inactive DMC1 and RAD51 due to lack of the HOP2–MND1 complex, exhibits a high level of chromosome synapsis and that most DSBs in these spermatocytes are repaired. This suggests that DSB repair catalyzed solely by HOP2 supports homologous chromosome pairing and synapsis. In addition, we show that in vitro HOP2 promotes the co-aggregation of ssDNA with duplex DNA, binds to ssDNA leading to unstacking of the bases, and promotes the formation of a three-strand synaptic intermediate. However, HOP2 shows distinctive mechanistic signatures as a recombinase. Namely, HOP2-mediated strand exchange does not require ATP and, in contrast to DMC1, joint molecules formed by HOP2 are more sensitive to mismatches and are efficiently dissociated by RAD54. We propose that HOP2 may act as a recombinase with specific functions in meiosis.

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Two telomeric ends of acrocentric chromosome play distinct roles in homologous chromosome synapsis in the fetal mouse oocyte

Chromosoma ◽

10.1007/s00412-021-00752-1 ◽

2021 ◽

Vol 130 (1) ◽

pp. 41-52

Author(s):

Parinaz Kazemi ◽

Teruko Taketo

Keyword(s):

Homologous Chromosome ◽

Acrocentric Chromosome ◽

Mouse Oocyte ◽

Fetal Mouse ◽

Chromosome Synapsis

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

10.1101/2021.08.04.455073 ◽

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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Homologous chromosome pairing in meiosis of higher eukaryotes—still an enigma?

Genome ◽

10.1139/gen-2019-0154 ◽

2020 ◽

Vol 63 (10) ◽

pp. 469-482

Author(s):

J. Sybenga

Keyword(s):

Chromosome Pairing ◽

Dna Sequences ◽

Homologous Chromosome ◽

Homology Search ◽

Size Difference ◽

Primary Role ◽

Dna Double Strand Breaks ◽

Homologous Chromosome Pairing ◽

Higher Eukaryotes

Meiosis is the basis of the generative reproduction of eukaryotes. The crucial first step is homologous chromosome pairing. In higher eukaryotes, micrometer-scale chromosomes, micrometer distances apart, are brought together by nanometer DNA sequences, at least a factor of 1000 size difference. Models of homology search, homologue movement, and pairing at the DNA level in higher eukaryotes are primarily based on studies with yeast where the emphasis is on the induction and repair of DNA double-strand breaks (DSB). For such a model, the very large nuclei of most plants and animals present serious problems. Homology search without DSBs cannot be explained by models based on DSB repair. The movement of homologues to meet each other and make contact at the molecular level is not understood. These problems are discussed and the conclusion is that at present practically nothing is known of meiotic homologue pairing in higher eukaryotes up to the formation of the synaptonemal complex, and that new, necessarily speculative models must be developed. Arguments are given that RNA plays a central role in homology search and a tentative model involving RNA in homology search is presented. A role of actin in homologue movement is proposed. The primary role of DSBs in higher eukaryotes is concluded to not be in pairing but in the preparation of Holliday junctions, ultimately leading to chromatid exchange.

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Noncanonical meiosis in the nematode Caenorhabditis elegans as a model for studying the molecular bases of the homologous chromosome synapsis, crossing over, and segregation

Russian Journal of Genetics ◽

10.1134/s102279541712002x ◽

2017 ◽

Vol 53 (12) ◽

pp. 1283-1298 ◽

Cited By ~ 1

Author(s):

Yu. F. Bogdanov

Keyword(s):

Caenorhabditis Elegans ◽

Homologous Chromosome ◽

Crossing Over ◽

Nematode Caenorhabditis Elegans ◽

Chromosome Synapsis ◽

Molecular Bases

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The role of the ameiotic1 gene in the initiation of meiosis and in subsequent meiotic events in maize.

Genetics ◽

10.1093/genetics/135.4.1151 ◽

1993 ◽

Vol 135 (4) ◽

pp. 1151-1166 ◽

Cited By ~ 3

Author(s):

I Golubovskaya ◽

Z K Grebennikova ◽

N A Avalkina ◽

W F Sheridan

Keyword(s):

Meiotic Division ◽

Higher Plants ◽

Gene Interaction ◽

Microtubule Organizing Center ◽

Spindle Fiber ◽

Chromosome Synapsis ◽

Organizing Center ◽

Relationship Of ◽

The Relationship

Abstract Understanding the initiation of meiosis and the relationship of this event with other key cytogenetic processes are major goals in studying the genetic control of meiosis in higher plants. Our genetic and structural analysis of two mutant alleles of the ameiotic1 gene (am1 and am1-praI) suggest that this locus plays an essential role in the initiation of meiosis in maize. The product of the ameiotic1 gene affects an earlier stage in the meiotic sequence than any other known gene in maize and is important for the irreversible commitment of cells to meiosis and for crucial events marking the passage from premeiotic interphase into prophase I including chromosome synapsis. It appears that the period of ameiotic1 gene function in meiosis at a minimum covers the interval from some point during premeiotic interphase until the early zygotene stage of meiosis. To study the interaction of genes in the progression of meiosis, several double meiotic mutants were constructed. In these double mutants (i) the ameiotic1 mutant allele was brought together with the meiotic mutation (afd1) responsible for the fixation of centromeres in meiosis; and with the mutant alleles of the three meiotic genes that control homologous chromosome segregation (dv1, ms43 and ms28), which impair microtubule organizing center organization, the orientation of the spindle fiber apparatus, and the depolymerization of spindle filaments after the first meiotic division, respectively; (ii) the afd1 mutation was combined with two mutations (dsy1 and as1) affecting homologous pairing; (iii) the ms43 mutation was combined with the as1, the ms28 and the dv1 mutations; and (iv) the ms28 mutation was combined with the dv1 mutation and the ms4 (polymitotic1) mutations. An analysis of gene interaction in the double mutants led us to conclude that the ameiotic1 gene is epistatic over the afd1, the dv1, the ms43 and the ms28 genes but the significance of this relationship requires further analysis. The afd gene appears to function from premeiotic interphase throughout the first meiotic division, but it is likely that its function begins after the start of the ameiotic1 gene expression. The afd1 gene is epistatic over the two synaptic mutations dsy1 and as1 and also over the dv1 mutation. The new ameiotic*-485 and leptotene arrest*-487 mutations isolated from an active Robertson's Mutator stocks take part in the control of the initiation of meiosis.

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Tex19.1 Regulates Meiotic DNA Double Strand Break Frequency in Mouse Spermatocytes

10.1101/099119 ◽

2017 ◽

Cited By ~ 4

Author(s):

James H. Crichton ◽

Christopher J. Playfoot ◽

Marie MacLennan ◽

David Read ◽

Howard J. Cooke ◽

...

Keyword(s):

Ubiquitin Ligase ◽

Meiotic Recombination ◽

Homologous Chromosome ◽

E3 Ubiquitin Ligase ◽

Double Strand Breaks ◽

Dna Double Strand Breaks ◽

Genetic Pathway ◽

Strand Breaks ◽

Chromosome Synapsis ◽

Meiotic Dsbs

AbstractMeiosis relies on the SPO11 endonuclease to generate the recombinogenic DNA double strand breaks (DSBs) required for homologous chromosome synapsis and segregation. The number of meiotic DSBs needs to be sufficient to allow chromosomes to search for and find their homologs, but not excessive to the point of causing genome instability. Here we report that meiotic DSB frequency in mouse spermatocytes is regulated by the mammal-specific gene Tex19.1. We show that the chromosome asynapsis previously reported in Tex19.1-/- spermatocytes is preceded by reduced numbers of recombination foci in leptotene and zygotene. Tex19.1 is required for the generation of normal levels of Spo11-dependent DNA damage during leptotene, but not for upstream events such as MEI4 foci formation or accumulation of H3K4me3 at recombination hotspots. Furthermore, we show that mice carrying mutations in the E3 ubiquitin ligase UBR2, a TEX19.1-interacting partner, phenocopy the Tex19.1-/- recombination defects. These data show that Tex19.1 and Ubr2 are required for mouse spermatocytes to generate sufficient meiotic DSBs to ensure that homology search is consistently successful, and reveal a hitherto unknown genetic pathway regulating meiotic DSB frequency in mammals.Author SummaryMeiosis is a specialised type of cell division that occurs during sperm and egg development to reduce chromosome number prior to fertilisation. Recombination is a key step in meiosis as it facilitates the pairing of homologous chromosomes prior to their reductional division, and generates new combinations of genetic alleles for transmission in the next generation. Regulating the amount of recombination is key for successful meiosis: too much will likely cause mutations, chromosomal re-arrangements and genetic instability, whereas too little causes defects in homologous chromosome pairing prior to the meiotic divisions. This study identifies a genetic pathway requiredto generate robust meiotic recombination in mouse spermatocytes. We show that male mice with mutations in Tex19.1 or Ubr2, which encodes an E3 ubiquitin ligase that interacts with TEX19.1, have defects in generating normal levels of meiotic recombination. We show that the defects in these mutants impact on the recombination process at the stage when programmed DNA double strand breaks are being made. This defect likely contributes to the chromosome synapsis and meiotic progression phenotypes previously described in these mutant mice. This study has implications for our understanding of how this fundamental aspect of genetics and inheritance is controlled.

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Cyclin B3 is dispensable for mouse spermatogenesis

10.1101/608315 ◽

2019 ◽

Cited By ~ 2

Author(s):

Mehmet E. Karasu ◽

Scott Keeney

Keyword(s):

Homologous Chromosome ◽

Histological Analysis ◽

Seminiferous Tubules ◽

Specific Expression ◽

Cyclin Dependent Kinases ◽

Meiotic Progression ◽

Chromosome Synapsis ◽

Cyclin E2 ◽

Sexual Production ◽

Cyclin B3

AbstractCyclins, as regulatory partners of cyclin-dependent kinases (CDKs), control the switch-like cell cycle transitions that orchestrate orderly duplication and segregation of genomes. Compared to mitosis, relatively little is known about how cyclin-CDK complexes control meiosis, the specialized cell division that generates gametes for sexual production. Mouse cyclin B3 was previously shown to have expression restricted to the beginning of meiosis, making it a candidate to regulate meiotic events. Indeed, female mice lacking cyclin B3 are sterile because oocytes arrest at the metaphase-to-anaphase transition of meiosis I. However, whether cyclin B3 functions during spermatogenesis was untested. Here, we found that males lacking cyclin B3 are fertile and show no detectable defects in spermatogenesis based on histological analysis of seminiferous tubules. Cytological analysis further showed no detectable defects in homologous chromosome synapsis or meiotic progression, and suggested that recombination is initiated and completed efficiently. Moreover, absence of cyclin B3 did not exacerbate previously described meiotic defects in mutants deficient for cyclin E2, suggesting a lack of redundancy between these cyclins. Thus, unlike in females, cyclin B3 is not essential for meiosis in males despite its prominent meiosis-specific expression.

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