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WormBook : the Online Review of C.... May 2017Sexual reproduction requires the production of haploid gametes (sperm and egg) with only one copy of each chromosome; fertilization then restores the diploid chromosome... (Review)
Review
Sexual reproduction requires the production of haploid gametes (sperm and egg) with only one copy of each chromosome; fertilization then restores the diploid chromosome content in the next generation. This reduction in genetic content is accomplished during a specialized cell division called meiosis, in which two rounds of chromosome segregation follow a single round of DNA replication. In preparation for the first meiotic division, homologous chromosomes pair and synapse, creating a context that promotes formation of crossover recombination events. These crossovers, in conjunction with sister chromatid cohesion, serve to connect the two homologs and facilitate their segregation to opposite poles during the first meiotic division. During the second meiotic division, which is similar to mitosis, sister chromatids separate; the resultant products are haploid cells that become gametes. In Caenorhabditis elegans (and most other eukaryotes) homologous pairing and recombination are required for proper chromosome inheritance during meiosis; accordingly, the events of meiosis are tightly coordinated to ensure the proper execution of these events. In this chapter, we review the seminal events of meiosis: pairing of homologous chromosomes, the changes in chromosome structure that chromosomes undergo during meiosis, the events of meiotic recombination, the differentiation of homologous chromosome pairs into structures optimized for proper chromosome segregation at Meiosis I, and the ultimate segregation of chromosomes during the meiotic divisions. We also review the regulatory processes that ensure the coordinated execution of these meiotic events during prophase I.
Topics: Animals; Caenorhabditis elegans; Cell Division; Chromosome Segregation; Chromosomes; Meiosis; Meiotic Prophase I; Recombination, Genetic
PubMed: 26694509
DOI: 10.1895/wormbook.1.178.1 -
Seminars in Cell & Developmental Biology Sep 2015Meiosis is one of the defining events in gametogenesis. Male and female germ cells both undergo one round of meiotic cell division during their development in order to... (Review)
Review
Meiosis is one of the defining events in gametogenesis. Male and female germ cells both undergo one round of meiotic cell division during their development in order to reduce the ploidy of the gametes, and thereby maintain the ploidy of the species after fertilisation. However, there are some aspects of meiosis in the female germline, such as the prolonged arrest in dictyate, that appear to predispose oocytes to missegregate their chromosomes and transmit aneuploidies to the next generation. These maternally-derived aneuploidies are particularly problematic in humans where they are major contributors to miscarriage, age-related infertility, and the high incidence of Down's syndrome in human conceptions. This review will discuss how events that occur in foetal oocyte development and during the oocytes' prolonged dictyate arrest can influence meiotic chromosome segregation and the incidence of aneuploidy in adult oocytes.
Topics: Animals; Chromosome Segregation; Crossing Over, Genetic; Female; Humans; Meiosis; Oocytes; Oogenesis; Recombination, Genetic; Trisomy
PubMed: 26454098
DOI: 10.1016/j.semcdb.2015.10.005 -
Cold Spring Harbor Perspectives in... May 2015Recombination is a prominent feature of meiosis in which it plays an important role in increasing genetic diversity during inheritance. Additionally, in most organisms,... (Review)
Review
Recombination is a prominent feature of meiosis in which it plays an important role in increasing genetic diversity during inheritance. Additionally, in most organisms, recombination also plays mechanical roles in chromosomal processes, most notably to mediate pairing of homologous chromosomes during prophase and, ultimately, to ensure regular segregation of homologous chromosomes when they separate at the first meiotic division. Recombinational interactions are also subject to important spatial patterning at both early and late stages. Recombination-mediated processes occur in physical and functional linkage with meiotic axial chromosome structure, with interplay in both directions, before, during, and after formation and dissolution of the synaptonemal complex (SC), a highly conserved meiosis-specific structure that links homolog axes along their lengths. These diverse processes also are integrated with recombination-independent interactions between homologous chromosomes, nonhomology-based chromosome couplings/clusterings, and diverse types of chromosome movement. This review provides an overview of these diverse processes and their interrelationships.
Topics: Animals; Chromosome Pairing; Chromosomes; DNA Breaks, Double-Stranded; Humans; Meiosis; Recombination, Genetic; Synaptonemal Complex
PubMed: 25986558
DOI: 10.1101/cshperspect.a016626 -
Human Reproduction Update Nov 2022Meiosis is an essential stage in the life cycle of sexually reproducing species, underlying formation of haploid gametes and serving as the basis of genetic diversity. A... (Review)
Review
BACKGROUND
Meiosis is an essential stage in the life cycle of sexually reproducing species, underlying formation of haploid gametes and serving as the basis of genetic diversity. A central mechanism of meiosis is recombination between homologous chromosomes, during which programmed DNA double-strand breaks (DSBs) are sequentially repaired to form the crossovers essential for faithful chromosomal segregation. Aberrant meiotic recombination often leads to gametogenic failure or produces aneuploid gametes resulting in subfertility or infertility, miscarriage or birth defects.
OBJECTIVE AND RATIONALE
The goal of this review was to characterize the molecular mechanisms of meiotic recombination and related human infertility disorders, particularly male infertility caused by non-obstructive azoospermia (NOA).
SEARCH METHODS
Our search included PubMed database articles, focusing mainly on English-language publications dated between January 2016 and February 2022. The search term 'meiosis' was combined with the following keywords: meiotic initiation, chromosome pairing, homologous recombination, chromosome axis, DSB, DSB repair, crossover, meiotic sex chromosome inactivation, meiotic checkpoints, meiotic arrest, NOA, premature ovarian insufficiency (POI) or premature ovarian failure, treatment and cancer. In addition, references within these articles were used to identify additional studies.
OUTCOMES
The preliminary search generated ∼3500 records. The majority of articles were identified as meeting abstracts or duplicates, contained non-English text or provided insufficient data and were therefore eliminated. A total of 271 articles associated with meiotic recombination were included in the final analysis. This review provides an overview of molecules and mechanisms involved in meiotic recombination processes, specifically meiosis-specific chromosome structures, DSB formation, homology search, formation of recombination intermediates and crossover formation. The cumulative results suggest that meiosis is regulated sequentially by a series of meiotic recombination genes and proteins. Importantly, mutations in these genes often affect meiotic progression, activating meiotic checkpoints, causing germ cell arrest and leading to subfertility or infertility. At least 26 meiotic recombination-related genes have been reported to be mutated in NOA in men, and 10 of these genes are mutated in POI in women. This suggests that variants of meiotic recombination-related genes can cause human subfertility or infertility, especially NOA.
WIDER IMPLICATIONS
Understanding the processes of homologous chromosome pairing, recombination and timely resolution of homologous chromosomes may provide guidance for the analysis of potential monogenetic causes of human subfertility or infertility and the development of personalized treatments. In clinical practice, we can develop a meiotic recombination-related gene panel to screen for gene mutations in individuals with subfertility or infertility. Testicular sperm extraction should not be recommended when an NOA-affected individual carries definite disease-causing mutations of a meiotic gene, so as to avoid the unnecessary invasive diagnosis. Risk of ovarian dysfunction should be evaluated if a woman carries meiotic recombination-related gene mutations. It may be possible to improve or restore fertility through manipulation of meiotic recombination-related genes in the future.
Topics: Humans; Male; Female; Azoospermia; Semen; Homologous Recombination; Reproduction
PubMed: 35613017
DOI: 10.1093/humupd/dmac024 -
Genes & Development Mar 2020To induce cell type-specific forms of gene regulation, pioneer factors open tightly packed, inaccessible chromatin sites, enabling the molecular machinery to act on... (Review)
Review
To induce cell type-specific forms of gene regulation, pioneer factors open tightly packed, inaccessible chromatin sites, enabling the molecular machinery to act on functionally significant information encoded in DNA. While previous studies of pioneer factors have revealed their functions in transcriptional regulation, pioneer factors that open chromatin for other physiological events remain undetermined. In this issue of , Spruce and colleagues (pp. 398-412) report the functional significance of a "pioneer complex" in mouse meiotic recombination. This complex, comprised of the zinc finger DNA-binding protein PRDM9 and the SNF2 family chromatin remodeler HELLS, exposes nucleosomal DNA to designate the sites of DNA double-strand breaks that initiate meiotic recombination. Both HELLS and PRDM9 are required for the determination of these recombination hot spots. Through the identification of a pioneer complex for meiotic recombination, this study broadens the conceptual scope of pioneer factors, indicating their functional significance in biological processes beyond transcriptional regulation.
Topics: Animals; DNA Helicases; Histone-Lysine N-Methyltransferase; Meiosis; Mice; Multiprotein Complexes; Nucleosomes; Recombination, Genetic
PubMed: 32122967
DOI: 10.1101/gad.336438.120 -
Comptes Rendus Biologies 2016Meiosis is a specialized cell division at the origin of the haploid cells that eventually develop into the gametes. It therefore lies at the heart of Mendelian heredity.... (Review)
Review
Meiosis is a specialized cell division at the origin of the haploid cells that eventually develop into the gametes. It therefore lies at the heart of Mendelian heredity. Recombination and redistribution of the homologous chromosomes arising during meiosis constitute an important source of genetic diversity, conferring to meiosis a particularly important place in the evolution and the diversification of the species. Our understanding of the molecular mechanisms governing meiotic recombination has considerably progressed these last decades, benefiting from complementary approaches led on various model species. An overview of these mechanisms will be provided as well as a discussion on the implications of these recent discoveries.
Topics: Animals; Chromosome Segregation; Chromosomes; Genetics; Humans; Meiosis; Recombination, Genetic
PubMed: 27180110
DOI: 10.1016/j.crvi.2016.04.003 -
Seminars in Cell & Developmental Biology Jun 2016The proper execution of meiotic recombination (or crossing over) is essential for chromosome segregation during the first meiotic division, and thus this process is... (Review)
Review
The proper execution of meiotic recombination (or crossing over) is essential for chromosome segregation during the first meiotic division, and thus this process is regulated by multiple, and often elaborate, mechanisms. Meiotic recombination begins with the programmed induction of DNA double-strand breaks (DSBs), of which only a subset are selected to be repaired into crossovers. This crossover selection process is carried out by a number of pro-crossover proteins that regulate the fashion in which DSBs are repaired. Here, we highlight recent studies regarding the process of DSB fate selection by a family of pro-crossover proteins known as the Zip-3 homologs.
Topics: Amino Acid Sequence; Animals; Crossing Over, Genetic; DNA Breaks, Double-Stranded; Humans; Meiosis
PubMed: 26806636
DOI: 10.1016/j.semcdb.2016.01.008 -
Trends in Genetics : TIG Aug 2021Mutation of the human genome results in three classes of genomic variation: single nucleotide variants; short insertions or deletions; and large structural variants... (Review)
Review
Mutation of the human genome results in three classes of genomic variation: single nucleotide variants; short insertions or deletions; and large structural variants (SVs). Some mutations occur during normal processes, such as meiotic recombination or B cell development, and others result from DNA replication or aberrant repair of breaks in sequence-specific contexts. Regardless of mechanism, mutations are subject to selection, and some hotspots can manifest in disease. Here, we discuss genomic regions prone to mutation, mechanisms contributing to mutation susceptibility, and the processes leading to their accumulation in normal and somatic genomes. With further, more accurate human genome sequencing, additional mutation hotspots, mechanistic details of their formation, and the relevance of hotspots to evolution and disease are likely to be discovered.
Topics: DNA Replication; Genome, Human; Genomic Structural Variation; Genomics; Humans; Mutation; Polymorphism, Single Nucleotide; Recombination, Genetic
PubMed: 33199048
DOI: 10.1016/j.tig.2020.10.003 -
Current Opinion in Plant Biology Oct 2019Meiotic recombination provides genetic diversity in populations and ensures accurate homologous chromosome segregation for genome integrity. During meiosis,... (Review)
Review
Meiotic recombination provides genetic diversity in populations and ensures accurate homologous chromosome segregation for genome integrity. During meiosis, recombination processes, from DNA double strand breaks (DSBs) to crossover formation are tightly linked to higher order chromosome structure, including chromatid cohesion, axial element formation, homolog pairing and synapsis. The extensive studies on plant meiosis have revealed the important conserved roles for meiotic proteins in homologous recombination. Recent works have focused on elucidating the mechanistic basis of how meiotic proteins regulate recombination events via protein complex formation and modifications such as phosphorylation, ubiquitination, and SUMOylation. Here, we highlight recent advances on the signaling and modifications of meiotic proteins that mediate the formation of DSBs and crossovers in plants.
Topics: Chromosome Pairing; DNA Breaks, Double-Stranded; DNA Repair; Homologous Recombination; Meiosis
PubMed: 31048232
DOI: 10.1016/j.pbi.2019.04.001 -
Trends in Genetics : TIG May 2019Despite the universal importance of meiotic recombination for generating genetic diversity, numbers and distribution of recombination events along chromosomes vary among... (Review)
Review
Despite the universal importance of meiotic recombination for generating genetic diversity, numbers and distribution of recombination events along chromosomes vary among species, genotypes within species, and between sexes. Some interspecies differences stem from the diversity of genome size and composition among eukaryotes. Large-genome species, such as humans and most crops, display recombination landscapes that are different from those of small-genome yeasts. Chromatin patterns, including histone modifications and DNA methylation, are also responsible for interspecies differences as well as differences between the sexes. Finally, despite the overall recombination pathway conservation, there are species-specific components that result in distinct recombination patterns. Consequently, characteristics that are defining for the recombination landscape and universally shared by all eukaryotes remain largely to be discovered.
Topics: Biodiversity; Chromatin; Crossing Over, Genetic; Genetic Association Studies; Homologous Recombination; Humans; Meiosis; Polyploidy; Recombination, Genetic; Species Specificity
PubMed: 30948240
DOI: 10.1016/j.tig.2019.02.002