Meiotic recombination

In the meiotic prophase, programmed DNA double-strand breaks are repaired by meiotic recombination. Recombination-defective meiocytes are eliminated to preserve genome integrity in gametes. BRCA1 is a critical protein in somatic homologous recombination, but studies have suggested that BRCA1 is dispensable for meiotic recombination. Here we show that BRCA1 is essential for meiotic recombination. Interestingly, BRCA1 also has a function in eliminating recombination-defective oocytes. Brca1 knockout (KO) rescues the survival of Dmc1 KO oocytes far more efficiently than removing CHK2, a vital component of the DNA damage checkpoint in oocytes...

BACKGROUND: Sex-limited chromosomes Y and W share some characteristics, including the degeneration of protein-coding genes, enrichment of repetitive elements, and heterochromatin. However, although many studies have suggested that Y chromosomes retain genes related to male function, far less is known about W chromosomes and whether they retain genes related to female-specific function. RESULTS: Here, we built a chromosome-level genome assembly of the Asian corn borer, Ostrinia furnacalis Guenée (Lepidoptera: Crambidae, Pyraloidea), an economically important pest in corn, from a female, including both the Z and W chromosome...

DNA double-strand breaks (DSBs) activate DNA damage responses (DDRs) in both mitotic and meiotic cells. A single-stranded DNA (ssDNA) binding protein, Replication protein-A (RPA) binds to the ssDNA formed at DSBs to activate ATR/Mec1 kinase for the response. Meiotic DSBs induce homologous recombination monitored by a meiotic DDR called the recombination checkpoint that blocks the pachytene exit in meiotic prophase I. In this study, we further characterized the essential role of RPA in the maintenance of the recombination checkpoint during Saccharomyces cerevisiae meiosis...

Chromosomal regions with meiotic drivers exhibit biased transmission (> 50 %) over their competing homologous chromosomal region. These regions often have two prominent genetic features: suppressed meiotic crossing over and rapidly evolving multicopy gene families. Heteromorphic sex chromosomes (e.g., XY) often share these two genetic features with chromosomal regions exhibiting meiotic drive. Here, we discuss parallels between meiotic drive and sex chromosome evolution, how the divergence of heteromorphic sex chromosomes can be influenced by meiotic drive, experimental approaches to study meiotic drive on sex chromosomes, and meiotic drive in traditional and non-traditional model organisms with high-quality genome assemblies...

DNA double-strand breaks (DSBs) are nucleolytically processed to generate single-stranded DNA tails for homologous recombination. In Saccharomyces cerevisiae meiosis, this 5'-to-3' resection involves initial nicking by the Mre11-Rad50-Xrs2 complex (MRX) plus Sae2, then exonucleolytic digestion by Exo1. Chromatin remodeling adjacent to meiotic DSBs is thought to be necessary for resection, but the relevant remodeling activity was unknown. Here we show that the SWI/SNF-like ATPase Fun30 plays a major, non-redundant role in resecting meiotic DSBs...

UNLABELLED: 53BP1 plays a crucial role in regulating DNA damage repair pathway choice and checkpoint signaling in somatic cells; however, its role in meiosis has remained enigmatic. In this study, we demonstrate that the Caenorhabditis elegans ortholog of 53BP1, HSR-9, associates with chromatin in both proliferating and meiotic germ cells. Notably, HSR-9 is enriched on the X chromosome pair in pachytene oogenic germ cells. HSR-9 is also present at kinetochores during both mitotic and meiotic divisions but does not appear to be essential for monitoring microtubule-kinetochore attachments or tension...

In meiotic cells, chromosomes are organized as chromatin loop arrays anchored to a protein axis. This organization is essential to regulate meiotic recombination, from DNA double-strand break (DSB) formation to their repair. In mammals, it is unknown how chromatin loops are organized along the genome and how proteins participating in DSB formation are tethered to the chromosome axes. Here, we identify three categories of axis-associated genomic sites: PRDM9 binding sites, where DSBs form; binding sites of the insulator protein CTCF; and H3K4me3-enriched sites...

The accurate segregation of homologous chromosomes during the Meiosis I reductional division in most sexually reproducing eukaryotes requires crossing over between homologs. In baker's yeast approximately 80 percent of meiotic crossovers result from Mlh1-Mlh3 and Exo1 acting to resolve double-Holliday junction (dHJ) intermediates in a biased manner. Little is known about how Mlh1-Mlh3 is recruited to recombination intermediates to perform its role in crossover resolution. We performed a gene dosage screen in baker's yeast to identify novel genetic interactors with Mlh1-Mlh3...

Sex chromosome aneuploidies are among the most common variations in human whole chromosome copy numbers, with an estimated prevalence in the general population of 1:400 to 1:1400 live births. Unlike whole-chromosome aneuploidies of autosomes, those of sex chromosomes, such as the 47, XXY aneuploidy that causes Klinefelter Syndrome (KS), often originate from the paternal side, caused by a lack of crossover (CO) formation between the X and Y chromosomes. COs must form between all chromosome pairs to pass meiotic checkpoints and are the product of meiotic recombination that occurs between homologous sequences of parental chromosomes...

UNLABELLED: The conserved Rad2/XPG family 5'-3' exonuclease, Exonuclease 1 (Exo1), plays many roles in DNA metabolism including during resolution of DNA double strand breaks (DSBs) via homologous recombination. Prior studies provided evidence that the end-resection activity of Exo1 is downregulated in yeast and mammals by Cdk1/2 family cyclin-dependent and checkpoint kinases, including budding yeast kinase Rad53 which functions in mitotic cells. Here we provide evidence that the master meiotic kinase Mek1, a paralogue of Rad53, limits 5'-3' single strand resection at the sites of programmed meiotic DNA breaks...

Robertsonian chromosomes form by fusion of two chromosomes that have centromeres located near their ends, known as acrocentric or telocentric chromosomes. This fusion creates a new metacentric chromosome and is a major mechanism of karyotype evolution and speciation. Robertsonian chromosomes are common in nature and were first described in grasshoppers by the zoologist W. R. B. Robertson more than 100 years ago. They have since been observed in many species, including catfish, sheep, butterflies, bats, bovids, rodents and humans, and are the most common chromosomal change in mammals...

A central basic feature of meiosis is pairing of homologous maternal and paternal chromosomes ("homologs") intimately along their lengths. Recognition between homologs and their juxtaposition in space are mediated by axis-associated DNA recombination complexes. Additional effects ensure that pairing occurs without ultimately giving entanglements among unrelated chromosomes. Here we examine the process of homolog juxtaposition in real time by 4D fluorescence imaging of tagged chromosomal loci at high spatio-temporal resolution in budding yeast...

Meiotic crossovers (COs) generate genetic diversity and are crucial for viable gamete production. Plant COs are typically limited to 1-3 per chromosome pair, constraining the development of improved varieties, which in wheat is exacerbated by an extreme distal localisation bias. Advances in wheat genomics and related technologies provide new opportunities to investigate, and possibly modify, recombination in this important crop species. Here, we investigate the disruption of FIGL1 in tetraploid and hexaploid wheat as a potential strategy for modifying CO frequency/position...

Programmed DNA double-strand break (DSB) formation is a crucial feature of meiosis in most organisms. DSBs initiate recombination-mediated linking of homologous chromosomes, which enables correct chromosome segregation in meiosis. DSBs are generated on chromosome axes by heterooligomeric focal clusters of DSB-factors. Whereas DNA-driven protein condensation is thought to assemble the DSB-machinery, its targeting to chromosome axes is poorly understood. We uncover in mice that efficient biogenesis of DSB-machinery clusters requires seeding by axial IHO1 platforms...

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Most DNA double-strand breaks (DSBs) are harmful to genome integrity. However, some forms of DSBs are essential to biological processes, such as meiotic recombination and V(D)J recombination. DSBs are also required for programmed DNA elimination (PDE) in ciliates and nematodes. In nematodes, the DSBs are healed with telomere addition. While telomere addition sites have been well-characterized, little is known regarding the DSBs that fragment nematode chromosomes. Here, we used embryos from the nematode Ascaris to study the timing of PDE breaks and examine the DSBs and their end processing...

Chromosomal fusions represent one of the most common types of chromosomal rearrangements found in nature. Yet, their role in shaping the genomic landscape of recombination and hence genome evolution remains largely unexplored. Here, we take advantage of wild mice populations with chromosomal fusions to evaluate the effect of this type of structural variant on genomic landscapes of recombination and divergence. To this aim, we combined cytological analysis of meiotic crossovers in primary spermatocytes with inferred analysis of recombination rates based on linkage disequilibrium using single nucleotide polymorphisms...

Recent developments in understanding the distribution and distinctive features of recombination hotspots are reviewed and approaches are proposed to increase recombination frequency in coldspot regions. Recombination events during meiosis provide the foundation and premise for creating new varieties of crops. The frequency of recombination in different genomic regions differs across eukaryote species, with recombination generally occurring more frequently at the ends of chromosomes. In most crop species, recombination is rare in centromeric regions...

The conserved MRE11-RAD50-NBS1/Xrs2 complex is crucial for DNA break metabolism and genome maintenance. While hypomorphic Rad50 mutation mice showed normal meiosis, both null and hypomorphic rad50 mutation yeast displayed impaired meiosis recombination. However, the in vivo function of Rad50 in mammalian germ cells, particularly its in vivo role in the resection of meiotic DSB ends at the molecular level remains elusive. Here, we established germ cell-specific Rad50 knockout mouse models to determine the role of Rad50 in mitosis and meiosis of mammalian germ cells...

RAD51 is the central eukaryotic recombinase required for meiotic recombination and mitotic repair of double-strand DNA breaks (DSBs)1,2 . However, the mechanism by which RAD51 functions at DSB sites in chromatin has remained elusive. Here we report the cryo-electron microscopy structures of human RAD51-nucleosome complexes, in which RAD51 forms ring and filament conformations. In the ring forms, the N-terminal lobe domains (NLDs) of RAD51 protomers are aligned on the outside of the RAD51 ring, and directly bind to the nucleosomal DNA...