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PLoS Genetics Apr 2017The meiosis-specific chromosomal events of homolog pairing, synapsis, and recombination occur over an extended meiotic prophase I that is many times longer than prophase...
The meiosis-specific chromosomal events of homolog pairing, synapsis, and recombination occur over an extended meiotic prophase I that is many times longer than prophase of mitosis. Here we show that, in mice, maintenance of an extended meiotic prophase I requires the gene Meioc, a germ-cell specific factor conserved in most metazoans. In mice, Meioc is expressed in male and female germ cells upon initiation of and throughout meiotic prophase I. Mouse germ cells lacking Meioc initiate meiosis: they undergo pre-meiotic DNA replication, they express proteins involved in synapsis and recombination, and a subset of cells progress as far as the zygotene stage of prophase I. However, cells in early meiotic prophase-as early as the preleptotene stage-proceed to condense their chromosomes and assemble a spindle, as if having progressed to metaphase. Meioc-deficient spermatocytes that have initiated synapsis mis-express CYCLIN A2, which is normally expressed in mitotic spermatogonia, suggesting a failure to properly transition to a meiotic cell cycle program. MEIOC interacts with YTHDC2, and the two proteins pull-down an overlapping set of mitosis-associated transcripts. We conclude that when the meiotic chromosomal program is initiated, Meioc is simultaneously induced so as to extend meiotic prophase. Specifically, MEIOC, together with YTHDC2, promotes a meiotic (as opposed to mitotic) cell cycle program via post-transcriptional control of their target transcripts.
Topics: Animals; Cell Cycle Proteins; Chromosome Pairing; Cyclin A2; Gene Expression Regulation, Developmental; Male; Meiosis; Mice; Mitosis; Prophase; RNA-Binding Proteins; Spermatocytes; Spermatogenesis; Spermatogonia
PubMed: 28380054
DOI: 10.1371/journal.pgen.1006704 -
Science (New York, N.Y.) Feb 2018Mitotic chromosomes fold as compact arrays of chromatin loops. To identify the pathway of mitotic chromosome formation, we combined imaging and Hi-C analysis of...
Mitotic chromosomes fold as compact arrays of chromatin loops. To identify the pathway of mitotic chromosome formation, we combined imaging and Hi-C analysis of synchronous DT40 cell cultures with polymer simulations. Here we show that in prophase, the interphase organization is rapidly lost in a condensin-dependent manner, and arrays of consecutive 60-kilobase (kb) loops are formed. During prometaphase, ~80-kb inner loops are nested within ~400-kb outer loops. The loop array acquires a helical arrangement with consecutive loops emanating from a central "spiral staircase" condensin scaffold. The size of helical turns progressively increases to ~12 megabases during prometaphase. Acute depletion of condensin I or II shows that nested loops form by differential action of the two condensins, whereas condensin II is required for helical winding.
Topics: Adenosine Triphosphatases; Animals; Cell Line; Chromosomes; Computational Biology; DNA-Binding Proteins; Genomics; Interphase; Mitosis; Multiprotein Complexes; Prometaphase; Prophase; Xenopus laevis
PubMed: 29348367
DOI: 10.1126/science.aao6135 -
Seminars in Cell & Developmental Biology Jun 2016The mycelial fungus Sordaria macrospora was first used as experimental system for meiotic recombination. This review shows that it provides also a powerful cytological... (Review)
Review
The mycelial fungus Sordaria macrospora was first used as experimental system for meiotic recombination. This review shows that it provides also a powerful cytological system for dissecting chromosome dynamics in wild-type and mutant meioses. Fundamental cytogenetic findings include: (1) the identification of presynaptic alignment as a key step in pairing of homologous chromosomes. (2) The discovery that biochemical complexes that mediate recombination at the DNA level concomitantly mediate pairing of homologs. (3) This pairing process involves not only resolution but also avoidance of chromosomal entanglements and the resolution system includes dissolution of constraining DNA recombination interactions, achieved by a unique role of Mlh1. (4) Discovery that the central components of the synaptonemal complex directly mediate the re-localization of the recombination proteins from on-axis to in-between homologue axis positions. (5) Identification of putative STUbL protein Hei10 as a structure-based signal transduction molecule that coordinates progression and differentiation of recombinational interactions at multiple stages. (6) Discovery that a single interference process mediates both nucleation of the SC and designation of crossover sites, thereby ensuring even spacing of both features. (7) Discovery of local modulation of sister-chromatid cohesion at sites of crossover recombination.
Topics: Chromosome Pairing; Fungal Proteins; Models, Biological; Recombination, Genetic; Sordariales; Synaptonemal Complex
PubMed: 26877138
DOI: 10.1016/j.semcdb.2016.02.012 -
Chromosoma Mar 2014Observations of a wide range of organisms show that the centromeres form associations of pairs or small groups at different stages of meiotic prophase. Little is known... (Review)
Review
Observations of a wide range of organisms show that the centromeres form associations of pairs or small groups at different stages of meiotic prophase. Little is known about the functions or mechanisms of these associations, but in many cases, synaptonemal complex elements seem to play a fundamental role. Two main associations are observed: homology-independent associations very early in the meiotic program-sometimes referred to as centromere coupling-and a later association of homologous centromeres, referred to as centromere pairing or tethering. The later centromere pairing initiates during synaptonemal complex assembly, then persists after the dissolution of the synaptonemal complex. While the function of the homology-independent centromere coupling remains a mystery, centromere pairing appears to have a direct impact on the chromosome segregation fidelity of achiasmatic chromosomes. Recent work in yeast, Drosophila, and mice suggest that centromere pairing is a previously unappreciated, general meiotic feature that may promote meiotic segregation fidelity of the exchange and non-exchange chromosomes.
Topics: Animals; Centromere; Chromosomes; Humans; Meiosis; Plants; Synaptonemal Complex
PubMed: 24126501
DOI: 10.1007/s00412-013-0439-4 -
Nucleic Acids Research Mar 2021In most taxa, halving of chromosome numbers during meiosis requires that homologous chromosomes (homologues) pair and form crossovers. Crossovers emerge from the...
In most taxa, halving of chromosome numbers during meiosis requires that homologous chromosomes (homologues) pair and form crossovers. Crossovers emerge from the recombination-mediated repair of programmed DNA double-strand breaks (DSBs). DSBs are generated by SPO11, whose activity requires auxiliary protein complexes, called pre-DSB recombinosomes. To elucidate the spatiotemporal control of the DSB machinery, we focused on an essential SPO11 auxiliary protein, IHO1, which serves as the main anchor for pre-DSB recombinosomes on chromosome cores, called axes. We discovered that DSBs restrict the DSB machinery by at least four distinct pathways in mice. Firstly, by activating the DNA damage response (DDR) kinase ATM, DSBs restrict pre-DSB recombinosome numbers without affecting IHO1. Secondly, in their vicinity, DSBs trigger IHO1 depletion mainly by another DDR kinase, ATR. Thirdly, DSBs enable homologue synapsis, which promotes the depletion of IHO1 and pre-DSB recombinosomes from synapsed axes. Finally, DSBs and three DDR kinases, ATM, ATR and PRKDC, enable stage-specific depletion of IHO1 from all axes. We hypothesize that these four negative feedback pathways protect genome integrity by ensuring that DSBs form without excess, are well-distributed, and are restricted to genomic locations and prophase stages where DSBs are functional for promoting homologue pairing and crossover formation.
Topics: ATPases Associated with Diverse Cellular Activities; Animals; Ataxia Telangiectasia Mutated Proteins; Cell Cycle Proteins; Chromosome Pairing; DNA Breaks, Double-Stranded; Feedback, Physiological; Gametogenesis; Meiosis; Mice; Pachytene Stage; Sex Chromosomes; Signal Transduction
PubMed: 33619545
DOI: 10.1093/nar/gkab082 -
A few of our favorite things: Pairing, the bouquet, crossover interference and evolution of meiosis.Seminars in Cell & Developmental Biology Jun 2016Meiosis presents many important mysteries that await elucidation. Here we discuss two such aspects. First, we consider how the current meiotic program might have... (Review)
Review
Meiosis presents many important mysteries that await elucidation. Here we discuss two such aspects. First, we consider how the current meiotic program might have evolved. We emphasize the central feature of this program: how homologous chromosomes find one another ("pair") so as to create the connections required for their regular segregation at Meiosis I. Points of emphasis include the facts that: (i) the classical "bouquet stage" is not required for initial homolog contacts in the current evolved meiotic program; and (ii) diverse observations point to commonality between molecules that mediate meiotic inter-homolog interactions and molecules that are integral to centromeres and/or to microtubule organizing centers (a.k.a. spindle pole bodies or centrosomes). Second, we provide an overview of the classical phenomenon of crossover (CO) interference in an effort to bridge the gap between description on the one hand versus logic and mechanism on the other.
Topics: Animals; Biological Evolution; Chromosome Pairing; Crossing Over, Genetic; Microtubule-Organizing Center
PubMed: 26927691
DOI: 10.1016/j.semcdb.2016.02.024 -
Cell Cycle (Georgetown, Tex.) 2018
Topics: Meiosis; Synaptonemal Complex
PubMed: 29233050
DOI: 10.1080/15384101.2017.1411435 -
PLoS Genetics Feb 2023Chromosome movements and licensing of synapsis must be tightly regulated during early meiosis to ensure accurate chromosome segregation and avoid aneuploidy, although...
Chromosome movements and licensing of synapsis must be tightly regulated during early meiosis to ensure accurate chromosome segregation and avoid aneuploidy, although how these steps are coordinated is not fully understood. Here we show that GRAS-1, the worm homolog of mammalian GRASP/Tamalin and CYTIP, coordinates early meiotic events with cytoskeletal forces outside the nucleus. GRAS-1 localizes close to the nuclear envelope (NE) in early prophase I and interacts with NE and cytoskeleton proteins. Delayed homologous chromosome pairing, synaptonemal complex (SC) assembly, and DNA double-strand break repair progression are partially rescued by the expression of human CYTIP in gras-1 mutants, supporting functional conservation. However, Tamalin, Cytip double knockout mice do not exhibit obvious fertility or meiotic defects, suggesting evolutionary differences between mammals. gras-1 mutants show accelerated chromosome movement during early prophase I, implicating GRAS-1 in regulating chromosome dynamics. GRAS-1-mediated regulation of chromosome movement is DHC-1-dependent, placing it acting within the LINC-controlled pathway, and depends on GRAS-1 phosphorylation at a C-terminal S/T cluster. We propose that GRAS-1 coordinates the early steps of homology search and licensing of SC assembly by regulating the pace of chromosome movement in early prophase I.
Topics: Animals; Humans; Mice; Caenorhabditis elegans; Caenorhabditis elegans Proteins; Chromosome Pairing; Chromosome Segregation; Mammals; Meiosis; Meiotic Prophase I; Synaptonemal Complex
PubMed: 36809245
DOI: 10.1371/journal.pgen.1010666 -
The Plant Cell Mar 2021The bipolar mitotic spindle is a highly conserved structure among eukaryotes that mediates chromosome alignment and segregation. Spindle assembly and size control are...
The bipolar mitotic spindle is a highly conserved structure among eukaryotes that mediates chromosome alignment and segregation. Spindle assembly and size control are facilitated by force-generating microtubule-dependent motor proteins known as kinesins. In animals, kinesin-12 cooperates with kinesin-5 to produce outward-directed forces necessary for spindle assembly. In plants, the relevant molecular mechanisms for spindle formation are poorly defined. While an Arabidopsis thaliana kinesin-5 ortholog has been identified, the kinesin-12 ortholog in plants remains elusive. In this study, we provide experimental evidence for the function of Arabidopsis KINESIN-12E in spindle assembly. In kinesin-12e mutants, a delay in spindle assembly is accompanied by the reduction of spindle size, demonstrating that KINESIN-12E contributes to mitotic spindle architecture. Kinesin-12E localization is mitosis-stage specific, beginning with its perinuclear accumulation during prophase. Upon nuclear envelope breakdown, KINESIN-12E decorates subpopulations of microtubules in the spindle and becomes progressively enriched in the spindle midzone. Furthermore, during cytokinesis, KINESIN-12E shares its localization at the phragmoplast midzone with several functionally diversified Arabidopsis KINESIN-12 members. Changes in the kinetochore and in prophase and metaphase spindle dynamics occur in the absence of KINESIN-12E, suggest it might play an evolutionarily conserved role during spindle formation similar to its spindle-localized animal kinesin-12 orthologs.
Topics: Arabidopsis; Kinesins; Kinetochores; Metaphase; Microtubules; Prophase
PubMed: 33751090
DOI: 10.1093/plcell/koaa003 -
Genes & Development Feb 2010Organisms that reproduce sexually must reduce their chromosome number by half during meiosis to generate haploid gametes. To achieve this reduction in ploidy, organisms... (Review)
Review
Organisms that reproduce sexually must reduce their chromosome number by half during meiosis to generate haploid gametes. To achieve this reduction in ploidy, organisms must devise strategies to couple sister chromatids so that they stay together during the first meiotic division (when homologous chromosomes separate) and then segregate away from one another during the second division. Here we review recent findings that shed light on how Caenorhabditis elegans, an organism with holocentric chromosomes, deals with these challenges of meiosis by differentiating distinct chromosomal subdomains and remodeling chromosome structure during prophase. Furthermore, we discuss how features of chromosome organization established during prophase affect later chromosome behavior during the meiotic divisions. Finally, we illustrate how analysis of holocentric meiosis can inform our thinking about mechanisms that operate on monocentric chromosomes.
Topics: Animals; Caenorhabditis elegans; Caenorhabditis elegans Proteins; Chromatids; Chromosome Pairing; Chromosomes; Meiosis; Models, Biological
PubMed: 20123904
DOI: 10.1101/gad.1863610