Ontology highlight
ABSTRACT:
PROVIDER: PRJNA944242 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR23851900_1.fastq.gz | Fastqsanger.gz | |||
| SRR23851900_2.fastq.gz | Fastqsanger.gz | |||
| SRR23852000_1.fastq.gz | Fastqsanger.gz | |||
| SRR23852000_2.fastq.gz | Fastqsanger.gz | |||
| SRR23852100_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 768 |
Similar Datasets
Project description:Meiotic recombination differs between males and females, however, when and how these differences are established is unknown. We identify extensive sex differences at recombination initiation by mapping hotspots of meiotic DNA double strand breaks in male and female mice. Contrary to past findings in humans, few hotspots are used uniquely in either sex. Instead, grossly different recombination landscapes result from up to 15-fold differences in hotspot use between males and females. Indeed, most recombination occurs at sex-biased hotspots. Sex biased hotspots appear to be partly determined by chromosome structure, and DNA methylation, absent in females at the onset of meiosis, plays a substantial role. Sex differences are also evident later in meiosis as the repair frequency of distal meiotic breaks as crossovers diverges in males and females. Suppression of distal crossovers may help to minimize age-related aneuploidy that arises due to cohesion loss during dictyate arrest in females.
2018-09-20 | GSE99921 | GEO
Project description:During meiosis, crossover recombination is essential to link homologous chromosomes and drive faithful chromosome segregation. Crossover recombination is non-random across the genome, and centromere-proximal crossovers are associated with an increased risk of aneuploidy, including Trisomy 21 in humans. Here, we identify the conserved Ctf19/CCAN kinetochore sub-complex as a major factor that minimizes potentially deleterious centromere-proximal crossovers in budding yeast. We uncover multi-layered suppression of pericentromeric recombination by the Ctf19 complex, operating across distinct chromosomal distances. The Ctf19 complex prevents meiotic DNA break formation, the initiating event of recombination, proximal to the centromere. The Ctf19 complex independently drives the enrichment of cohesin throughout the broader pericentromere to suppress crossovers, but not DNA breaks. This non-canonical role of the kinetochore in defining a chromosome domain that is refractory to crossovers adds a new layer of functionality by which the kinetochore prevents the incidence of chromosome segregation errors that generate aneuploid gametes.
2015-12-15 | GSE72683 | GEO
Project description:During the repair of DNA double-strand breaks (DSBs), de novo synthesized DNA strand can displace the parental strand to generate single-strand DNA (ssDNA) flaps. Many programmed DSBs and thus many ssDNA flaps occur during meiosis. However, how these flaps are removed remains enigmatic. Here, we show that meiosis-specific depletion of Dna2 (dna2-md) in Saccharomyces cerevisiae causes an abundant accumulation of RPA-ssDNA flaps and an expansion of RPA from DSBs to broader regions. As a result, DSB repair is defective and spores are inviable, although the levels of crossovers/non-crossovers seem to be unaffected. Furthermore, inducing Dna2 expression at pachytene is highly effective in removing accumulated RPA and restoring spore viability. Moreover, the depletion of Pif1, an activator of polymerase δ required for meiotic recombination-associated DNA synthesis, and Pif1 inhibitor Mlh2 decreased and increased RPA accumulation in dna2-md, respectively. Together, our findings show that meiotic DSB repair requires Dna2 to remove RPA-ssDNA flaps generated from meiotic recombination-associated DNA synthesis. Additionally, we showed that Dna2 also regulates DSB-independent RPA distribution.
2023-08-30 | GSE217628 | GEO
Project description:During meiosis, crossover recombination is essential to link homologous chromosomes and drive faithful chromosome segregation. Crossover recombination is non-random across the genome, and centromere-proximal crossovers are associated with an increased risk of aneuploidy, including Trisomy 21 in humans. Here, we identify the conserved Ctf19/CCAN kinetochore sub-complex as a major factor that minimizes potentially deleterious centromere-proximal crossovers in budding yeast. We uncover multi-layered suppression of pericentromeric recombination by the Ctf19 complex, operating across distinct chromosomal distances. The Ctf19 complex prevents meiotic DNA break formation, the initiating event of recombination, proximal to the centromere. The Ctf19 complex independently drives the enrichment of cohesin throughout the broader pericentromere to suppress crossovers, but not DNA breaks. This non-canonical role of the kinetochore in defining a chromosome domain that is refractory to crossovers adds a new layer of functionality by which the kinetochore prevents the incidence of chromosome segregation errors that generate aneuploid gametes. Two samples total: two biological replicate Spo11-oligo maps of S. cerevisiae SK1 mcm21 null mutant
2015-12-15 | E-GEOD-72683 | biostudies-arrayexpress
Project description:DNA double-strand breaks (DSBs) are introduced in meiosis to initiate recombination and to generate crossovers, the reciprocal exchanges of genetic material between parental chromosomes. Here we present the first high-resolution map of meiotic DSBs in individual human genomes. Comparing DSB maps between individuals shows that along with DNA binding by PRDM9, additional factors dictate the efficiency of DSB formation. Furthermore, we find that in human males, the frequency of DSB formation is the primary determinant of crossover rate. Patterns of sequence polymorphisms around meiotic DSB hotspots provide evidence for both GC-biased gene conversion and for a mutagenic role of DSB repair and/or recombination. Finally, we provide compelling evidence that the aberrant repair of meiotic DSBs is a driver of human genomic disorders. Detection of meiotic double strand breaks in testis of several human male individuals.
2014-11-17 | E-GEOD-59836 | biostudies-arrayexpress
Project description:DNA double-strand breaks (DSBs) are introduced in meiosis to initiate recombination and to generate crossovers, the reciprocal exchanges of genetic material between parental chromosomes. Here we present the first high-resolution map of meiotic DSBs in individual human genomes. Comparing DSB maps between individuals shows that along with DNA binding by PRDM9, additional factors dictate the efficiency of DSB formation. Furthermore, we find that in human males, the frequency of DSB formation is the primary determinant of crossover rate. Patterns of sequence polymorphisms around meiotic DSB hotspots provide evidence for both GC-biased gene conversion and for a mutagenic role of DSB repair and/or recombination. Finally, we provide compelling evidence that the aberrant repair of meiotic DSBs is a driver of human genomic disorders.
2014-11-17 | GSE59836 | GEO
Project description:Meiotic recombination in mammals requires recombination hotspot activation through the action of the histone 3 lysine-4 and lysine-36 methyltransferase PRDM9 to ensure successful double-strand break initiation and repair. Here using a Ewsr1 male germ cell conditional knockout mouse, we show that EWSR1 increases the efficiency of PRDM9-dependent H3K4/K36 trimethylation at the adjacent nucleosomes in vivo, and directs the hotspot choices for double-strand breaks formation and their subsequent repair into sufficient number of crossovers properly positioned along the centromere-telomere axis.
2020-12-17 | GSE108259 | GEO
Project description:A hallmark of meiosis is the rearrangement of parental alleles to assure genetic diversity in gametes. These chromosome rearrangements are mediated by the repair of programmed DNA double-strand-breaks (DSBs) as genetic crossovers between parental homologs. In mice, humans, and many other mammals, meiotic DSB occur primarily at hotspots, determined by sequence-specific binding of the PRDM9 protein. Without PRDM9, meiotic DSBs occur near gene promoters and other functional sites. Studies in a limited number of mouse strains showed that functional PRDM9 is required to complete meiosis, but despite its apparent importance, Prdm9 has been repeatedly lost across many animal lineages. Both the reason for mouse sterility in the absence of PRDM9 and the mechanism by which Prdm9 can be lost remain unclear. Here, we explore if mice can tolerate the loss of Prdm9. By generating Prdm9 functional knockouts in an array of genetic backgrounds, we observe a wide range of fertility phenotypes and ultimately demonstrate that PRDM9 is not required for completion of meiosis. Although DSBs still form at a common subset of functional sites in all mice lacking PRDM9, meiotic outcomes differ substantially. We speculate that DSBs at functional sites are difficult to repair as a crossover and that by increasing the efficiency of crossover formation at these sites, genetic modifiers of recombination rates can allow for meiotic progression. This model implies that species with a sufficiently high recombination rate may lose Prdm9 yet remain fertile.
2019-06-07 | GSE109874 | GEO
Project description:The DNA double strand breaks (DSBs) that initiate meiotic recombination are formed in the context of the meiotic chromosome axis, which in budding yeast contains a meiosis-specific cohesin isoform and the meiosis-specific proteins Hop1 and Red1. Hop1 and Red are important for DSB formation; DSB levels are reduced in their absence and their levels, which vary along the lengths of chromosomes, are positively correlated with DSB levels. How axis protein levels influence DSB formation and recombination remains unclear. To address this question, we developed a novel approach that uses a bacterial ParB-parS partition system to recruit axis proteins at high levels to inserts at recombination coldspots where Hop1 and Red1 levels are normally low. Recruiting Hop1 markedly increased DSBs and homologous recombination at target loci, to levels equivalent to those observed at endogenous recombination hotspots. This local increase in DSBs did not require Red1 or the meiosis-specific cohesin component Rec8, indicating that, of the axis proteins, Hop1 is sufficient to promote DSB formation. However, while most crossovers at endogenous recombination hotspots are formed by the meiosis-specific MutLγ resolvase, only a small fraction of crossovers that formed at an insert locus required MutLγ, regardless of whether or not Hop1 was recruited to that locus. Thus, while local Hop1 levels determine local DSB levels, the recombination pathways that repair these breaks can be determined by other factors, raising the intriguing possibility that different recombination pathways operate in different parts of the genome.
2022-07-12 | GSE201240 | GEO
Project description:In most eukaryotes, meiotic crossovers are essential for error-free chromosome segregation but are specifically repressed near centromeres to prevent missegregation. Recognized for >85 years, the molecular mechanism of this repression has remained unknown. Meiotic chromosomes contain two distinct cohesin complexes: pericentric complex (for segregation) and chromosomal arm complex (for crossing-over). We show that the pericentric-specific complex also actively represses pericentric meiotic double-strand break (DSB) formation and, consequently, crossovers. The fission yeast pericentric regions contain heterochromatin, removal of which can result in derepression in double-strand break formation and recombination during meiosis. We uncover the mechanism by which fission yeast heterochromatin protein Swi6 (mammalian HP1-homolog) prevents recruitment of activators of meiotic DSB formation such as Rec10. Localizing these missing activators to wild-type pericentromeres bypasses repression and generates abundant crossovers but reduces gamete viability.The molecular mechanism elucidated here likely extends to other species including humans, where pericentric crossovers can result in disorders such as Down syndrome. These mechanistic insights provide new clues to understand the roles played by multiple cohesin complexes, especially in human infertility and birth defects.
2018-06-14 | GSE115726 | GEO