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Methods in Molecular Biology (Clifton,... 2020Recombination and pairing are prominent features of meiosis where they play an important role in increasing genetic diversity. In most organisms recombination also plays...
Recombination and pairing are prominent features of meiosis where they play an important role in increasing genetic diversity. In most organisms recombination also plays mechanical roles in mediating pairing of homologous chromosomes during prophase and in ensuring regular segregation of homologous pairs at the first meiotic division. The laboratory directed by D. von Wettstein identified six key steps in the meiotic process: (1) Recombination mediated processes occur in physical and functional linkage with the synaptonemal complex (SC), a highly conserved, meiosis-specific structure that links homologous axes along their lengths. (2) The pairing process involves formation and resolution of chromosomal entanglements/interlockings. (3) The SC normally forms specifically between homologous chromosomes, but in unusual situations can form between nonhomologous chromosomes or regions resulting in two-phase SC formation. (4) In hexaploid common wheat, extensive multivalents form with multiple, pairing partner shifts, indicating homology recognition and SC formation among homoeologs as well as homologs. (5) Linkage between recombination and the SC is revealed by crossover-correlated nodules localized in the SC central region. (6) Modified SCs sometimes play a direct role in homolog segregation, providing the required connection between homologs in absence of crossovers/chiasmata.
Topics: Chromosome Pairing; Meiosis; Polyploidy; Recombination, Genetic; Triticum
PubMed: 32277447
DOI: 10.1007/978-1-0716-0356-7_2 -
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 -
Genetics Nov 2014Homology-dependent exchange of genetic information between DNA molecules has a profound impact on the maintenance of genome integrity by facilitating error-free DNA... (Review)
Review
Homology-dependent exchange of genetic information between DNA molecules has a profound impact on the maintenance of genome integrity by facilitating error-free DNA repair, replication, and chromosome segregation during cell division as well as programmed cell developmental events. This chapter will focus on homologous mitotic recombination in budding yeast Saccharomyces cerevisiae. However, there is an important link between mitotic and meiotic recombination (covered in the forthcoming chapter by Hunter et al. 2015) and many of the functions are evolutionarily conserved. Here we will discuss several models that have been proposed to explain the mechanism of mitotic recombination, the genes and proteins involved in various pathways, the genetic and physical assays used to discover and study these genes, and the roles of many of these proteins inside the cell.
Topics: DNA Damage; DNA, Fungal; Genetic Techniques; Mitosis; Recombination, Genetic; Saccharomyces cerevisiae
PubMed: 25381364
DOI: 10.1534/genetics.114.166140 -
Current Opinion in Plant Biology Apr 2017Meiotic recombination ensures the fertility of gametes and creates novel genetic combinations. Although meiotic crossover (CO) frequency is under homeostatic control, CO... (Review)
Review
Meiotic recombination ensures the fertility of gametes and creates novel genetic combinations. Although meiotic crossover (CO) frequency is under homeostatic control, CO frequency is also plastic in nature and can respond to environmental conditions. Most investigations have focused on temperature and recombination, but other external and internal stimuli also have important roles in modulating CO frequency. Even less is understood about the molecular mechanisms that underly these phenomenon, but recent work has begun to advance our knowledge in this field. In this review, we identify and explore potential mechanisms including changes in: the synaptonemal complex, chromatin state, DNA methylation, and RNA splicing.
Topics: Animals; Crossing Over, Genetic; DNA Methylation; Meiosis; Stress, Physiological; Synaptonemal Complex
PubMed: 28258986
DOI: 10.1016/j.pbi.2016.11.019 -
Seminars in Cell & Developmental Biology Jun 2016The molecular details of meiotic recombination have been determined for a small number of model organisms. From these studies, a general picture has emerged that shows... (Review)
Review
The molecular details of meiotic recombination have been determined for a small number of model organisms. From these studies, a general picture has emerged that shows that most, if not all, recombination is initiated by a DNA double-strand break (DSB) that is repaired in a recombinogenic process using a homologous DNA strand as a template. However, the details of recombination vary between organisms, and it is unknown which variant is representative of evolutionarily primordial meiosis or most prevalent among eukaryotes. To answer these questions and to obtain a better understanding of the range of recombination processes among eukaryotes, it is important to study a variety of different organisms. Here, the ciliate Tetrahymena thermophila is introduced as a versatile meiotic model system, which has the additional bonus of having the largest phylogenetic distance to all of the eukaryotes studied to date. Studying this organism can contribute to our understanding of the conservation and diversification of meiotic recombination processes.
Topics: Crossing Over, Genetic; DNA Breaks, Double-Stranded; DNA Repair; Meiosis; Models, Biological; Tetrahymena
PubMed: 26899715
DOI: 10.1016/j.semcdb.2016.02.021 -
Molecular Cell Oct 2021Currently favored models for meiotic recombination posit that both noncrossover and crossover recombination are initiated by DNA double-strand breaks but form by...
Currently favored models for meiotic recombination posit that both noncrossover and crossover recombination are initiated by DNA double-strand breaks but form by different mechanisms: noncrossovers by synthesis-dependent strand annealing and crossovers by formation and resolution of double Holliday junctions centered around the break. This dual mechanism hypothesis predicts different hybrid DNA patterns in noncrossover and crossover recombinants. We show that these predictions are not upheld, by mapping with unprecedented resolution parental strand contributions to recombinants at a model locus. Instead, break repair in both noncrossovers and crossovers involves synthesis-dependent strand annealing, often with multiple rounds of strand invasion. Crossover-specific double Holliday junction formation occurs via processes involving branch migration as an integral feature, one that can be separated from repair of the break itself. These findings reveal meiotic recombination to be a highly dynamic process and prompt a new view of the relationship between crossover and noncrossover recombination.
Topics: Crossing Over, Genetic; DNA Breaks, Double-Stranded; DNA, Cruciform; DNA, Fungal; Meiosis; Recombinational DNA Repair; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins; Sister Chromatid Exchange; Templates, Genetic
PubMed: 34453891
DOI: 10.1016/j.molcel.2021.08.003 -
Cold Spring Harbor Perspectives in... Oct 2014The generation of haploid gametes by meiosis is a highly conserved process for sexually reproducing organisms that, in almost all cases, involves the extensive breakage... (Review)
Review
The generation of haploid gametes by meiosis is a highly conserved process for sexually reproducing organisms that, in almost all cases, involves the extensive breakage of chromosomes. These chromosome breaks occur during meiotic prophase and are essential for meiotic recombination as well as the subsequent segregation of homologous chromosomes. However, their formation and repair must be carefully monitored and choreographed with nuclear dynamics and the cell division program to avoid the creation of aberrant chromosomes and defective gametes. It is becoming increasingly clear that an intricate checkpoint-signaling network related to the canonical DNA damage response is deeply interwoven with the meiotic program and preserves order during meiotic prophase. This meiotic checkpoint network (MCN) creates a wide range of dependent relationships controlling chromosome movement, chromosome pairing, chromatin structure, and double-strand break (DSB) repair. In this review, we summarize our current understanding of the MCN. We discuss commonalities and differences in different experimental systems, with a particular emphasis on the emerging design principles that control and limit cross talk between signals to ultimately ensure the faithful inheritance of chromosomes by the next generation.
Topics: Apoptosis; Cell Cycle Checkpoints; Chromosome Pairing; DNA Breaks, Double-Stranded; DNA Repair; DNA Replication; Models, Genetic; Prophase; Recombination, Genetic; Signal Transduction
PubMed: 25274702
DOI: 10.1101/cshperspect.a016675 -
Genetics Mar 2018A century of genetic studies of the meiotic process in females has been greatly augmented by both modern molecular biology and major advances in cytology. These... (Review)
Review
A century of genetic studies of the meiotic process in females has been greatly augmented by both modern molecular biology and major advances in cytology. These approaches, and the findings they have allowed, are the subject of this review. Specifically, these efforts have revealed that meiotic pairing in females is not an extension of somatic pairing, but rather occurs by a poorly understood process during premeiotic mitoses. This process of meiotic pairing requires the function of several components of the synaptonemal complex (SC). When fully assembled, the SC also plays a critical role in maintaining homolog synapsis and in facilitating the maturation of double-strand breaks (DSBs) into mature crossover (CO) events. Considerable progress has been made in elucidating not only the structure, function, and assembly of the SC, but also the proteins that facilitate the formation and repair of DSBs into both COs and noncrossovers (NCOs). The events that control the decision to mature a DSB as either a CO or an NCO, as well as determining which of the two CO pathways (class I or class II) might be employed, are also being characterized by genetic and genomic approaches. These advances allow a reconsideration of meiotic phenomena such as interference and the centromere effect, which were previously described only by genetic studies. In delineating the mechanisms by which the oocyte controls the number and position of COs, it becomes possible to understand the role of CO position in ensuring the proper orientation of homologs on the first meiotic spindle. Studies of bivalent orientation have occurred in the context of numerous investigations into the assembly, structure, and function of the first meiotic spindle. Additionally, studies have examined the mechanisms ensuring the segregation of chromosomes that have failed to undergo crossing over.
Topics: Animals; Centromere; Chromosome Painting; Chromosome Pairing; Chromosome Segregation; Crossing Over, Genetic; DNA Breaks, Double-Stranded; Drosophila melanogaster; Female; Meiosis; Oocytes; Recombination, Genetic; Spindle Apparatus; Synaptonemal Complex
PubMed: 29487146
DOI: 10.1534/genetics.117.300081 -
FEBS Letters Oct 2019The primary function of cyclin-dependent kinases (CDKs) in complex with their activating cyclin partners is to promote mitotic division in somatic cells. This canonical... (Review)
Review
The primary function of cyclin-dependent kinases (CDKs) in complex with their activating cyclin partners is to promote mitotic division in somatic cells. This canonical cell cycle-associated activity is also crucial for fertility as it allows the proliferation and differentiation of stem cells within the reproductive organs to generate meiotically competent cells. Intriguingly, several CDKs exhibit meiosis-specific functions and are essential for the completion of the two reductional meiotic divisions required to generate haploid gametes. These meiosis-specific functions are mediated by both known CDK/cyclin complexes and meiosis-specific CDK-regulators and are important for a variety of processes during meiotic prophase. The majority of meiotic defects observed upon deletion of these proteins occur during the extended prophase I of the first meiotic division. Importantly a lack of redundancy is seen within the meiotic arrest phenotypes described for many of these proteins, suggesting intricate layers of cell cycle control are required for normal meiotic progression. Using the process of male germ cell development (spermatogenesis) as a reference, this review seeks to highlight the diverse roles of selected CDKs their activators, and their regulators during gametogenesis.
Topics: Animals; Cell Cycle Checkpoints; Cell Differentiation; Cell Proliferation; Cyclin-Dependent Kinases; Cyclins; Gene Expression Regulation; Haploidy; Male; Meiosis; Mice; Nuclear Proteins; Recombination, Genetic; Signal Transduction; Spermatogenesis; Spermatozoa; Stem Cells
PubMed: 31566717
DOI: 10.1002/1873-3468.13627 -
Biomolecules Nov 2022Meiotic recombination is a pivotal event that ensures faithful chromosome segregation and creates genetic diversity in gametes. Meiotic recombination is initiated by... (Review)
Review
Meiotic recombination is a pivotal event that ensures faithful chromosome segregation and creates genetic diversity in gametes. Meiotic recombination is initiated by programmed double-strand breaks (DSBs), which are catalyzed by the conserved Spo11 protein. Spo11 is an enzyme with structural similarity to topoisomerase II and induces DSBs through the nucleophilic attack of the phosphodiester bond by the hydroxy group of its tyrosine (Tyr) catalytic residue. DSBs caused by Spo11 are repaired by homologous recombination using homologous chromosomes as donors, resulting in crossovers/chiasmata, which ensure physical contact between homologous chromosomes. Thus, the site of meiotic recombination is determined by the site of the induced DSB on the chromosome. Meiotic recombination is not uniformly induced, and sites showing high recombination rates are referred to as recombination hotspots. In fission yeast, , a nonsense point mutation of is a well-characterized meiotic recombination hotspot caused by the heptanucleotide sequence 5'-ATGACGT-3' at the mutation point. In this review, we summarize the meiotic recombination mechanisms revealed by the analysis of the fission gene as a model system.
Topics: Schizosaccharomyces; Homologous Recombination; Schizosaccharomyces pombe Proteins; Models, Biological
PubMed: 36551189
DOI: 10.3390/biom12121761