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Annual Review of Genetics Nov 2023The raison d'ĂȘtre of meiosis is shuffling of genetic information via Mendelian segregation and, within individual chromosomes, by DNA crossing-over. These outcomes are... (Review)
Review
The raison d'ĂȘtre of meiosis is shuffling of genetic information via Mendelian segregation and, within individual chromosomes, by DNA crossing-over. These outcomes are enabled by a complex cellular program in which interactions between homologous chromosomes play a central role. We first provide a background regarding the basic principles of this program. We then summarize the current understanding of the DNA events of recombination and of three processes that involve whole chromosomes: homolog pairing, crossover interference, and chiasma maturation. All of these processes are implemented by direct physical interaction of recombination complexes with underlying chromosome structures. Finally, we present convergent lines of evidence that the meiotic program may have evolved by coupling of this interaction to late-stage mitotic chromosome morphogenesis.
Topics: Chromosome Pairing; Meiosis; Chromosomes; DNA; Chromosome Segregation; Crossing Over, Genetic
PubMed: 37788458
DOI: 10.1146/annurev-genet-061323-044915 -
Nucleic Acids Research May 2023Meiotic recombinases RAD51 and DMC1 mediate strand exchange in the repair of DNA double-strand breaks (DSBs) by homologous recombination. This is a landmark event of...
Meiotic recombinases RAD51 and DMC1 mediate strand exchange in the repair of DNA double-strand breaks (DSBs) by homologous recombination. This is a landmark event of meiosis that ensures genetic diversity in sexually reproducing organisms. However, the regulatory mechanism of DMC1/RAD51-ssDNA nucleoprotein filaments during homologous recombination in mammals has remained largely elusive. Here, we show that SPIDR (scaffold protein involved in DNA repair) regulates the assembly or stability of RAD51/DMC1 on ssDNA. Knockout of Spidr in male mice causes complete meiotic arrest, accompanied by defects in synapsis and crossover formation, which leads to male infertility. In females, loss of Spidr leads to subfertility; some Spidr-/- oocytes are able to complete meiosis. Notably, fertility is rescued partially by ablation of the DNA damage checkpoint kinase CHK2 in Spidr-/- females but not in males. Thus, our study identifies SPIDR as an essential meiotic recombination factor in homologous recombination in mammals.
Topics: Animals; Male; Mice; Cell Cycle Proteins; Chromosome Pairing; DNA Repair; Homologous Recombination; Mammals; Meiosis; Mice, Knockout; Rad51 Recombinase
PubMed: 36938872
DOI: 10.1093/nar/gkad154 -
Science (New York, N.Y.) Nov 2021Centromeres attach chromosomes to spindle microtubules during cell division and, despite this conserved role, show paradoxically rapid evolution and are typified by...
Centromeres attach chromosomes to spindle microtubules during cell division and, despite this conserved role, show paradoxically rapid evolution and are typified by complex repeats. We used long-read sequencing to generate the Col-CEN genome assembly that resolves all five centromeres. The centromeres consist of megabase-scale tandemly repeated satellite arrays, which support CENTROMERE SPECIFIC HISTONE H3 (CENH3) occupancy and are densely DNA methylated, with satellite variants private to each chromosome. CENH3 preferentially occupies satellites that show the least amount of divergence and occur in higher-order repeats. The centromeres are invaded by retrotransposons, which disrupt genetic and epigenetic organization. Centromeric crossover recombination is suppressed, yet low levels of meiotic DNA double-strand breaks occur that are regulated by DNA methylation. We propose that centromeres are evolving through cycles of satellite homogenization and retrotransposon-driven diversification.
Topics: Arabidopsis; Centromere; Chromosomes, Plant; DNA Methylation; DNA, Satellite; Epigenesis, Genetic; Evolution, Molecular; Genome, Plant; Histones; Meiosis; Recombination, Genetic; Retroelements; Sequence Analysis, DNA
PubMed: 34762468
DOI: 10.1126/science.abi7489 -
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 -
PLoS Genetics Nov 2019Balancer chromosomes are multiply inverted and rearranged chromosomes that are widely used in Drosophila genetics. First described nearly 100 years ago, balancers are... (Review)
Review
Balancer chromosomes are multiply inverted and rearranged chromosomes that are widely used in Drosophila genetics. First described nearly 100 years ago, balancers are used extensively in stock maintenance and complex crosses. Recently, the complete molecular structures of several commonly used balancers were determined by whole-genome sequencing. This revealed a surprising amount of variation among balancers derived from a common progenitor, identified genes directly affected by inversion breakpoints, and cataloged mutations shared by balancers. These studies emphasized that it is important to choose the optimal balancer, because different inversions suppress meiotic recombination in different chromosomal regions. In this review, we provide a brief history of balancers in Drosophila, discuss how they are used today, and provide examples of unexpected recombination events involving balancers that can lead to stock breakdown.
Topics: Animals; Centromere; Chromosome Inversion; Chromosomes, Insect; Drosophila melanogaster; Genome, Insect; Heterochromatin; Homologous Recombination; Phenotype; Sequence Deletion; X Chromosome
PubMed: 31697682
DOI: 10.1371/journal.pgen.1008421 -
Current Topics in Developmental Biology 2023Chromosomes adopt specific conformations to regulate various cellular processes. A well-documented chromosome configuration is the highly compacted chromosome structure... (Review)
Review
Chromosomes adopt specific conformations to regulate various cellular processes. A well-documented chromosome configuration is the highly compacted chromosome structure during metaphase. More regional chromatin conformations have also been reported, including topologically associated domains encompassing mega-bases of DNA and local chromatin loops formed by kilo-bases of DNA. In this review, we discuss the changes in chromatin conformation taking place between somatic and meiotic cells, with a special focus on the establishment of a proteinaceous structure, called the chromosome axis, at the beginning of meiosis. The chromosome axis is essential to support key meiotic processes such as chromosome pairing, homologous recombination, and balanced chromosome segregation to transition from a diploid to a haploid stage. We review the role of the chromosome axis in meiotic chromatin organization and provide a detailed description of its protein composition. We also review the conserved and distinct roles between species of axis proteins in meiotic recombination, which is a major factor contributing to the creation of genetic diversity and genome evolution. Finally, we discuss situations where the chromosome axis is deregulated and evaluate the effects on genome integrity and the consequences from protein deregulation in meiocytes exposed to heat stress, and aberrant expression of genes encoding axis proteins in mammalian somatic cells associated with certain types of cancers.
Topics: Animals; Synaptonemal Complex; Meiosis; Chromosome Pairing; Chromatin; Neoplasms; Mammals
PubMed: 36681479
DOI: 10.1016/bs.ctdb.2022.04.008 -
Frontiers in Cellular and Infection... 2021While most fungi have the ability to reproduce sexually, multiple independent lineages have lost meiosis and developed parasexual cycles in its place. Emergence of... (Review)
Review
While most fungi have the ability to reproduce sexually, multiple independent lineages have lost meiosis and developed parasexual cycles in its place. Emergence of parasexual cycles is particularly prominent in medically relevant fungi from the CUG paraphyletic group of species. Since the discovery of parasex in roughly two decades ago, it has served as the model for species. Importantly, parasex in retains hallmarks of meiosis including genetic recombination and chromosome segregation, making it a potential driver of genetic diversity. Furthermore, key meiotic genes play similar roles in parasex and highlights parallels between these processes. Yet, the evolutionary role of parasex in adaptation and the extent of resulting genotypic and phenotypic diversity remain as key knowledge gaps in this facultative reproductive program. Here, we present our current understanding of parasex, the mechanisms governing its regulation, and its relevance to biology.
Topics: Biological Evolution; Candida; Candida albicans; Genotype; Meiosis
PubMed: 34966696
DOI: 10.3389/fcimb.2021.796929 -
PLoS Genetics Jul 2021The presence of meiosis, which is a conserved component of sexual reproduction, across organisms from all eukaryotic kingdoms, strongly argues that sex is a primordial... (Review)
Review
The presence of meiosis, which is a conserved component of sexual reproduction, across organisms from all eukaryotic kingdoms, strongly argues that sex is a primordial feature of eukaryotes. However, extant meiotic structures and processes can vary considerably between organisms. The ciliated protist Tetrahymena thermophila, which diverged from animals, plants, and fungi early in evolution, provides one example of a rather unconventional meiosis. Tetrahymena has a simpler meiosis compared with most other organisms: It lacks both a synaptonemal complex (SC) and specialized meiotic machinery for chromosome cohesion and has a reduced capacity to regulate meiotic recombination. Despite this, it also features several unique mechanisms, including elongation of the nucleus to twice the cell length to promote homologous pairing and prevent recombination between sister chromatids. Comparison of the meiotic programs of Tetrahymena and higher multicellular organisms may reveal how extant meiosis evolved from proto-meiosis.
Topics: Chromosome Painting; Epigenesis, Genetic; Meiosis; Reproduction; Tetrahymena thermophila
PubMed: 34264933
DOI: 10.1371/journal.pgen.1009627 -
Nucleus (Austin, Tex.) Dec 2024Heterochromatin is an organizational property of eukaryotic chromosomes, characterized by extensive DNA and histone modifications, that is associated with the silencing... (Review)
Review
Heterochromatin is an organizational property of eukaryotic chromosomes, characterized by extensive DNA and histone modifications, that is associated with the silencing of transposable elements and repetitive sequences. Maintaining heterochromatin is crucial for ensuring genomic integrity and stability during the cell cycle. During meiosis, heterochromatin is important for homologous chromosome synapsis, recombination, and segregation, but our understanding of meiotic heterochromatin formation and condensation is limited. In this review, we focus on the dynamics and features of heterochromatin and how it condenses during meiosis in plants. We also discuss how meiotic heterochromatin influences the interaction and recombination of homologous chromosomes during prophase I.
Topics: Heterochromatin; Centromere; Meiosis; Chromosome Pairing
PubMed: 38488152
DOI: 10.1080/19491034.2024.2328719 -
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