-
ELife Jan 2021Protein modification by SUMO helps orchestrate the elaborate events of meiosis to faithfully produce haploid gametes. To date, only a handful of meiotic SUMO targets...
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.
Topics: Chromosome Pairing; Meiosis; Prophase; SUMO-1 Protein; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins; Sumoylation
PubMed: 33502312
DOI: 10.7554/eLife.57720 -
Reproductive Biology and Endocrinology... Oct 2023In human female primordial germ cells, the transition from mitosis to meiosis begins from the fetal stage. In germ cells, meiosis is arrested at the diplotene stage of... (Review)
Review
In human female primordial germ cells, the transition from mitosis to meiosis begins from the fetal stage. In germ cells, meiosis is arrested at the diplotene stage of prophase in meiosis I (MI) after synapsis and recombination of homologous chromosomes, which cannot be segregated. Within the follicle, the maintenance of oocyte meiotic arrest is primarily attributed to high cytoplasmic concentrations of cyclic adenosine monophosphate (cAMP). Depending on the specific species, oocytes can remain arrested for extended periods of time, ranging from months to even years. During estrus phase in animals or the menstrual cycle in humans, the resumption of meiosis occurs in certain oocytes due to a surge of luteinizing hormone (LH) levels. Any factor interfering with this process may lead to impaired oocyte maturation, which in turn affects female reproductive function. Nevertheless, the precise molecular mechanisms underlying this phenomenon has not been systematically summarized yet. To provide a comprehensive understanding of the recently uncovered regulatory network involved in oocyte development and maturation, the progress of the cellular and molecular mechanisms of oocyte nuclear maturation including meiosis arrest and meiosis resumption is summarized. Additionally, the advancements in understanding the molecular cytoplasmic events occurring in oocytes, such as maternal mRNA degradation, posttranslational regulation, and organelle distribution associated with the quality of oocyte maturation, are reviewed. Therefore, understanding the pathways regulating oocyte meiotic arrest and resumption will provide detailed insight into female reproductive system and provide a theoretical basis for further research and potential approaches for novel disease treatments.
Topics: Animals; Female; Humans; Oogenesis; Oocytes; Meiosis; Meiotic Prophase I; Ovarian Follicle
PubMed: 37784186
DOI: 10.1186/s12958-023-01143-0 -
G3 (Bethesda, Md.) Feb 2021Homoeologous recombination, aneuploidy, and other genetic changes are common in resynthesized allopolyploid Brassica napus. In contrast, the chromosomes of cultivars...
Homoeologous recombination, aneuploidy, and other genetic changes are common in resynthesized allopolyploid Brassica napus. In contrast, the chromosomes of cultivars have long been considered to be meiotically stable. To gain a better understanding of the underlying mechanisms leading to stabilization in the allopolyploid, the behavior of chromosomes during meiosis can be compared by unambiguous chromosome identification between resynthesized and natural B. napus. Compared with natural B. napus, resynthesized lines show high rates of nonhomologous centromere association, homoeologous recombination leading to translocation, homoeologous chromosome replacement, and association and breakage of 45S rDNA loci. In both natural and resynthesized B. napus, we observed low rates of univalents, A-C bivalents, and early sister chromatid separations. Reciprocal homoeologous chromosome exchanges and double reductions were photographed for the first time in meiotic telophase I. Meiotic errors were non-uniformly distributed across the genome in resynthesized B. napus, and in particular homoeologs sharing synteny along their entire length exhibited multivalents at diakinesis and polysomic inheritance at telophase I. Natural B. napus appeared to resolve meiotic errors mainly by suppressing homoeologous pairing, resolving nonhomologous centromere associations and 45S rDNA associations before diakinesis, and reducing homoeologous cross-overs.
Topics: Aneuploidy; Brassica napus; Chromosomes, Plant; Genome, Plant; Meiosis; Polyploidy
PubMed: 33704431
DOI: 10.1093/g3journal/jkaa011 -
ELife Feb 2022The phosphatidylinositol 3' kinase (PI3K)-related kinase ATR is crucial for mammalian meiosis. ATR promotes meiotic progression by coordinating key events in DNA repair,...
The phosphatidylinositol 3' kinase (PI3K)-related kinase ATR is crucial for mammalian meiosis. ATR promotes meiotic progression by coordinating key events in DNA repair, meiotic sex chromosome inactivation (MSCI), and checkpoint-dependent quality control during meiotic prophase I. Despite its central roles in meiosis, the ATR-dependent meiotic signaling network remains largely unknown. Here, we used phosphoproteomics to define ATR signaling events in testes from mice following chemical and genetic ablation of ATR signaling. Quantitative analysis of phosphoproteomes obtained after germ cell-specific genetic ablation of the ATR activating 9-1-1 complex or treatment with ATR inhibitor identified over 14,000 phosphorylation sites from testes samples, of which 401 phosphorylation sites were found to be dependent on both the 9-1-1 complex and ATR. Our analyses identified ATR-dependent phosphorylation events in crucial DNA damage signaling and DNA repair proteins including TOPBP1, SMC3, MDC1, RAD50, and SLX4. Importantly, we identified ATR and RAD1-dependent phosphorylation events in proteins involved in mRNA regulatory processes, including SETX and RANBP3, whose localization to the sex body was lost upon ATR inhibition. In addition to identifying the expected ATR-targeted S/T-Q motif, we identified enrichment of an S/T-P-X-K motif in the set of ATR-dependent events, suggesting that ATR promotes signaling via proline-directed kinase(s) during meiosis. Indeed, we found that ATR signaling is important for the proper localization of CDK2 in spermatocytes. Overall, our analysis establishes a map of ATR signaling in mouse testes and highlights potential meiotic-specific actions of ATR during prophase I progression.
Topics: Animals; Ataxia Telangiectasia Mutated Proteins; DNA Damage; DNA Repair; Male; Meiosis; Mice, Inbred C57BL; Morpholines; Phosphorylation; Proteome; Pyrimidines; RNA, Messenger; Signal Transduction; Spermatocytes; Testis; Mice
PubMed: 35133275
DOI: 10.7554/eLife.68648 -
Frontiers in Plant Science 2022is an allopolyploid with a genome constitution of StStYYHH (2 = 6 = 42). Highly frequent intergenomic translocations and chromosomal variations with repeat...
is an allopolyploid with a genome constitution of StStYYHH (2 = 6 = 42). Highly frequent intergenomic translocations and chromosomal variations with repeat amplification and deletions in have been identified in the previous studies. However, more complicated structural variations such as chromosomal inversions or intra-genomic translocations are still unknown in this species, so does the reason for the origin of the chromosomal variations. Heterozygotes with rearranged chromosomes always present irregular meiosis behaviors, which subsequently cause the secondary chromosome rearrangements. Investigation on the meiosis of heterozygotes, especially on the individual chromosome level, may provide the important clues to identify the more complicated chromosome structural variations in the populations, and clarify the origin of the chromosome variations. In this study, meiotic analysis was conducted on a heterozygote plant of , which showed high intra- and inter-genome chromosomal variations, by sequential fluorescence hybridization (FISH) and genomic hybridization (GISH), with each chromosome clearly recognized. The results showed chromosomal abnormalities at every meiotic stage and abnormalities in frequency variations between different sub-genomes and different individual chromosomes. The abnormalities were revealed as univalent, fragment, rod, or Y shape bivalent in diakinesis; univalent and rod bivalent in metaphase I; lagged and segregated chromatid, bridge, fragment of the sister chromatid, fragment, bridge accompanied with fragment, and unequal segregated chromosome in anaphase I; bridge and lagged chromatid in ana-telophase II; and micronucleus at uninucleate stage. Generally, the St and H genomes harbor more abnormalities than the Y genome. Moreover, a paracentric inversion in 2St was exclusively determined, and another paracentric inversion in 6Y was tentatively identified. In addition, novel deletions were clearly detected in 3H, 4H, 1Y, and 3Y homologous chromosomes; in particular, pericentric inversion in 3H was repeatedly identified in metaphase I. The study revealed the chromosomal inversions pre-existed in parents or populations, as well as inversions and deletions originated in the meiosis of the heterozygote in . Moreover, it indicated wide range of meiosis abnormalities on different stages and different chromosomes, and suggests that secondary rearrangements contribute much to the chromosome variations in .
PubMed: 35592580
DOI: 10.3389/fpls.2022.895437 -
Frontiers in Plant Science 2022Meiotic crossovers (COs) not only generate genetic diversity but also ensure the accuracy of homologous chromosome segregation. Here, we identified FIGNL1 as a new...
Meiotic crossovers (COs) not only generate genetic diversity but also ensure the accuracy of homologous chromosome segregation. Here, we identified FIGNL1 as a new inhibitor for extra crossover formation in rice. The mutant displays abnormal interactions between non-homologous chromosomes at diakinesis, and chromosome bridges and fragmentation at subsequent stages of meiosis, but shows normal homologous chromosome pairing and synapsis during early prophase I. FIGNL1 participates in homologous chromosome recombination and functions downstream of DMC1. Mutation of increases the number of bivalents in mutants, but does not change the number of HEI10 foci, indicating that FIGNL1 functions in limiting class II CO formation. FIGNL1 interacts with MEICA1, and colocalizes with MEICA1 in a dynamic pattern as punctate foci located between two linear homologous chromosomes. The localization of FIGNL1 depends on ZEP1-mediated assembly of the synaptonemal complex. Based on these results, we propose that FIGNL1 inhibits non-homologous chromosome interaction and CO formation during rice meiosis.
PubMed: 35898226
DOI: 10.3389/fpls.2022.945893 -
Sheng Li Xue Bao : [Acta Physiologica... Feb 2020Meiosis is a special type of cell division to produce haploid gametes with intact genome. The behavior of homologous chromosomes during the first division (meiosis... (Review)
Review
Meiosis is a special type of cell division to produce haploid gametes with intact genome. The behavior of homologous chromosomes during the first division (meiosis prophase I) is the most prominent feature of meiosis. During meiosis prophase I, synaptonemal complex (SC) formed between homologous chromosomes to promote the initiation and repair of programmed DNA double-strand breaks (DSBs), which is necessary for the correct recognition, pairing, recombination and separation of homologous chromosomes. In this paper, we reviewed the recent research progress on the composition and function of SC, discussed how the assembly of SC affected the repair of DSBs, and also summarized the known mutations on SC genes which were responsible for human reproductive disorders. On this basis, we also explored the future research direction of this field.
Topics: DNA Breaks, Double-Stranded; DNA Repair; Humans; Meiotic Prophase I; Synaptonemal Complex
PubMed: 32099986
DOI: No ID Found -
Cellular and Molecular Life Sciences :... Dec 2021In mammalian male meiosis, the heterologous X and Y chromosomes remain unsynapsed and, as a result, are subject to meiotic sex chromosome inactivation (MSCI). MSCI is... (Review)
Review
In mammalian male meiosis, the heterologous X and Y chromosomes remain unsynapsed and, as a result, are subject to meiotic sex chromosome inactivation (MSCI). MSCI is required for the successful completion of spermatogenesis. Following the initiation of MSCI, the X and Y chromosomes undergo various epigenetic modifications and are transformed into a nuclear body termed the XY body. Here, we review the mechanisms underlying the initiation of two essential, sequential processes in meiotic prophase I: MSCI and XY-body formation. The initiation of MSCI is directed by the action of DNA damage response (DDR) pathways; downstream of the DDR, unique epigenetic states are established, leading to the formation of the XY body. Accumulating evidence suggests that MSCI and subsequent XY-body formation may be driven by phase separation, a physical process that governs the formation of membraneless organelles and other biomolecular condensates. Thus, here we gather literature-based evidence to explore a phase separation hypothesis for the initiation of MSCI and the formation of the XY body.
Topics: Animals; DNA Damage; DNA Repair; Dosage Compensation, Genetic; Humans; Meiosis; Models, Biological; Sex Chromosomes
PubMed: 34971404
DOI: 10.1007/s00018-021-04075-3 -
BioRxiv : the Preprint Server For... Dec 2023Meiotic progression requires coordinated assembly and disassembly of protein complexes involved in chromosome synapsis and meiotic recombination. The AAA+ ATPase TRIP13...
Meiotic progression requires coordinated assembly and disassembly of protein complexes involved in chromosome synapsis and meiotic recombination. The AAA+ ATPase TRIP13 and its orthologue Pch2 are instrumental in remodeling HORMA domain proteins. Meiosis-specific HORMAD proteins are associated with unsynapsed chromosome axes but depleted from the synaptonemal complex (SC) of synapsed chromosome homologues. Here we report that TRIP13 localizes to the synapsed SC in early pachytene spermatocytes and to telomeres throughout meiotic prophase I. Loss of TRIP13 leads to meiotic arrest and thus sterility in both sexes. -null meiocytes exhibit abnormal persistence of HORMAD1 and HOMRAD2 on synapsed SC and chromosome asynapsis that preferentially affects XY and centromeric ends. These findings confirm the previously reported phenotypes of the hypomorph alleles. heterozygous () mice also exhibit meiotic defects that are less severe than the -null mice, showing that TRIP13 is a dosage-sensitive regulator of meiosis. Localization of TRIP13 to the synapsed SC is independent of SC axial element proteins such as REC8 and SYCP2/SYCP3. The N- or C-terminal FLAG-tagged TRIP13 proteins are functional and recapitulate the localization of native TRIP13 to SC and telomeres in knockin mice. Therefore, the evolutionarily conserved localization of TRIP13/Pch2 to the synapsed chromosomes provides an explanation for dissociation of HORMA domain proteins upon chromosome synapsis in diverse organisms.
PubMed: 37808842
DOI: 10.1101/2023.09.25.559355 -
Cell Jun 2020Meiosis is the specialized cell division that generates haploid gametes and is therefore essential for sexual reproduction. This SnapShot encompasses key events taking...
Meiosis is the specialized cell division that generates haploid gametes and is therefore essential for sexual reproduction. This SnapShot encompasses key events taking place during prophase I of meiosis that are required for achieving proper chromosome segregation and highlights how these are both conserved and diverged throughout five different species. To view this SnapShot, open or download the PDF.
Topics: Animals; Arabidopsis; Caenorhabditis elegans; Chromosome Segregation; Drosophila melanogaster; Meiosis; Meiotic Prophase I; Mice; Saccharomyces cerevisiae
PubMed: 32531249
DOI: 10.1016/j.cell.2020.04.038