Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Spo11-oligo mapping in S. cerevisiae Ctf19/CCAN kinetochore sub-complex mutant mcm21

ABSTRACT: 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.

ORGANISM(S): Saccharomyces cerevisiae

PROVIDER: GSE72683 | GEO | 2015/12/15

SECONDARY ACCESSION(S): PRJNA294661

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Spo11-oligo mapping in S. cerevisiae Ctf19/CCAN kinetochore sub-complex mutant mcm21

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

A meiotic XPF-ERCC1-like complex recognizes joint molecule recombination intermediates to promote crossover formation

Project description:Meiotic crossover formation requires the stabilization of early recombination intermediates by a set of proteins and occurs within the environment of the chromosome axis, a structure important for the regulation of meiotic recombination events. The molecular mechanisms underlying and connecting crossover recombination and axis localization are elusive. Here, we identified the ZZS (Zip2–Zip4–Spo16) complex, required for crossover formation, which carries two distinct activities: one provided by Zip4, which acts as hub through physical interactions with components of the chromosome axis and the crossover machinery, and the other carried by Zip2 and Spo16, which preferentially bind branched DNA molecules in vitro. We found that Zip2 and Spo16 share structural similarities to the structure-specific XPF–ERCC1 nuclease, although it lacks endonuclease activity. The XPF domain of Zip2 is required for crossover formation, suggesting that, together with Spo16, it has a noncatalytic DNA recognition function. Our results suggest that the ZZS complex shepherds recombination intermediates toward crossovers as a dynamic structural module that connects recombination events to the chromosome axis. The identification of the ZZS complex improves our understanding of the various activities required for crossover implementation and is likely applicable to other organisms, including mammals.

2018-02-14 | GSE103877 | GEO

Bub1 and CENP-U redundantly recruit Plk1 to stabilize kinetochore-microtubule attachments and ensure accurate chromosome segregation

Project description:Bub1 is required for the kinetochore/centromere localization of two essential mitotic kinases Plk1 and Aurora B. Surprisingly, stable depletion of Bub1 by ~95% in human cells marginally affects whole chromosome segregation fidelity. We show that CENP-U, which is recruited to kinetochores by the CENP-P and CENP-Q subunits of the CENP-O complex, is required to prevent chromosome mis-segregation in Bub1-depleted cells. Mechanistically, Bub1 and CENP-U redundantly recruit Plk1 to kinetochores to stabilize kinetochore-microtubule attachments, thereby ensuring accurate chromosome segregation. Furthermore, unlike its budding yeast homolog, the CENP-O complex does not regulate centromeric localization of Aurora B. Consistently, depletion of Bub1 or CENP-U sensitizes cells to the inhibition of Plk1 but not Aurora B kinase activity. Taken together, our findings provide mechanistic insight into the regulation of kinetochore function, which may have implications for targeted treatment of cancer cells with mutations perturbing kinetochore recruitment of Plk1 by Bub1 or the CENP-O complex.

2021-08-29 | GSE182827 | GEO

A conserved germline-specific Dsn1 alternative splice isoform supports oocyte and embryo development

Project description:Alternative RNA splicing can generate distinct protein isoforms to allow for the differential control of cell processes across cell types. The chromosome segregation and cell division programs associated with somatic mitosis and germline meiosis display dramatic differences such as kinetochore orientation, cohesin removal, or the presence of a gap phase. These changes in chromosome segregation require alterations to the established cell division machinery. However, it remains unclear what aspects of kinetochore function and its regulatory control differ between the mitotic and meiotic cell divisions to rewire these core processes. Additionally, the alternative splice isoforms that differentially modulate distinct cell division programs have remained elusive. Here, we demonstrate that mammalian germ cells express an alternative mRNA splice isoform for the kinetochore component, DSN1, a subunit of the MIS12 complex that links the centromeres to spindle microtubules during chromosome segregation. This germline DSN1 isoform bypasses the requirement for Aurora kinase phosphorylation for its centromere localization due to the absence of a key regulatory region allowing DSN1 to display persistent centromere localization. Expression of the germline DSN1 isoform in somatic cells results in constitutive kinetochore localization, chromosome segregation errors, and growth defects, providing an explanation for its tight cell type-specific expression. Reciprocally, precisely eliminating expression of the germline-specific DSN1 splice isoform in mouse models disrupts oocyte maturation and early embryonic divisions coupled with a reduction in fertility. Together, this work identifies a germline-specific splice isoform for a chromosome segregation component and implicates its role in mammalian fertility.

2024-08-28 | PXD054119 | Pride

The proteomic landscape of centromeric chromatin reveals an essential role for the Ctf19 complex in meiotic kinetochore assembly.

Project description:Faithful gamete formation during meiosis requires that kinetochores take on new functions that impact homolog pairing/recombination and their attachments to microtubules. We used a proteomics pipeline to determine the global composition of centromeric chromatin and kinetochores at distinct meiotic stages. Our datasets uncover an unanticipated role for the Ctf19CCAN inner kinetochore sub-complex in gametogenesis. We show that components of the Ctf19 complex that are dispensable for mitotic growth become critical for assembly of a functional kinetochore upon meiotic entry. Consequently, in the absence of these factors, chromosomes fail to attach to meiotic spindles and produce inviable gametes due to gross segregation errors. Our evidence suggests that functional kinetochore assembly is driven by Ctf19CCAN complex-dependent Ipl1AURORA B positioning at the inner kinetochore. Thus, our global view of kinetochore composition in meiosis reveals the extent of kinetochore remodelling during gametogenesis and uncovers a kinetochore assembly pathway that becomes critical in meiosis.

2021-02-23 | PXD019754 | Pride

Real-time dynamics of Plasmodium Ndc80 reveals unusual modes of chromosome segregation during parasite proliferative stages

Project description:Eukaryotic cell proliferation requires chromosome replication and precise segregation to ensure daughter cells have identical genomic copies. The genus Plasmodium, the causative agent of malaria, has developed remarkable characteristic of nuclear division throughout its lifecycle to meet some peculiar and unique challenges of DNA replication and chromosome segregation. The parasite undergoes atypical endomitosis and endoreduplication with an intact nuclear membrane and intranuclear mitotic spindle. To understand diverse modes of cell division in Plasmodium we have studied the behaviour and composition of a key part of the mitotic apparatus, the outer kinetochore Ndc80 complex that attaches the centromere of chromosomes to the microtubules of the mitotic spindle. Using Ndc80 live-cell imaging in Plasmodium berghei we observe dynamic changes throughout proliferative life-stages including highly unusual kinetochore arrangements in sexual stages of the parasite. Furthermore, we identify a divergent Spc24 component of Ndc80 complex, previously thought to be missing, and completing a canonical, albeit unusual, Ndc80 complex structure. Altogether our studies reveal the kinetochore as an ideal starting point towards understanding non-canonical modes of chromosome segregation and cell division in Plasmodium.

2020-06-09 | PXD017619 | Pride

Negative supercoil senses temperature to modulate meiotic crossovers and chromosomes

Project description:Crossover recombination is a hallmark of meiosis, which holds the paternal and maternal chromosomes (homologs) together for their faithful separation, meanwhile, it promotes genetic diversity of progenies. The pattern of crossover is mainly controlled by the architecture of meiotic chromosomes. Environmental factors, especially temperature, also play an important role in modulating crossovers. However, it is unclear how temperature affects crossovers. Here, we examined the distributions of budding yeast axis components (Red1, Hop1, and Rec8) and the CO-associated Zip3 foci in detail in different temperatures, and found that both increased and decreased temperatures result in shorter meiotic chromosome axes and more crossovers. Further investigations showed that altered temperature coordinately enhanced the hyperabundant accumulation of Hop1 and Red1 on chromosomes and the number of Zip3 foci. Most importantly, temperature-induced alterations in axis distribution and Zip3 foci depend on the changes in DNA negative supercoil. These findings suggest that yeast meiosis senses temperature changes by increasing the level of negative supercoil to increase crossovers and modulate chromosome organization. These findings provide a novel view in understanding the effect and mechanism of temperature on meiosis recombination and chromosome organization, and thus also have an important implication in evolution and breeding.

2024-07-30 | GSE246901 | GEO

The conserved SUMO ligase Zip3 protein associates differentially with meiotic double-strand break sites and reveals regional variations in the outcome of meiotic recombination

Project description:In meiosis, an excess number of DNA double-strand breaks (DSBs), the initiating DNA lesion, is formed compared to the number of crossovers, one of their repair products that creates the physical links between homologs and allows their correct segregation. It is not known if all DSB hotspots are also crossover hotspots, or if the ratio between DSB and crossovers varies with the chromosomal location. Here, to systematically investigate variation in the DSB/crossover ratio, we have established the genome-wide map of the Zip3 protein binding sites in budding yeast meiosis. We show that Zip3 associates with DSB sites when these are engaged into repair by crossing over, and that Zip3 binding frequency at DSB reflects its tendency to be repaired as a crossover. We further show that the relative amount of Zip3 per DSB varies with the chromosomal location and identify chromosomal features associated with high or low Zip3 per DSB ratio. Among these is the negative regulation by proximity to a centromere and positive by the proximity to axis-associated sequences. This work opens interesting perspectives to understand the role of these extra DSB that are not frequently used for crossover and our findings may extend to mammals that have a large excess of DSB compared to crossovers.

2013-12-18 | GSE40563 | GEO

AOCM-CPC - Kinetochores are macromolecular protein complexes that ensure accurate chromosome segregation by linking chromosomes to spindle microtubules and integrating safeguard mechanisms

Project description:Kinetochores are macromolecular protein complexes that ensure accurate chromosome segregation by linking chromosomes to spindle microtubules and integrating safeguard mechanisms. In yeast, the inner kinetochore, also known as Constitutive Centromere Associated Network (CCAN), is specifically established at point centromeres and has been implicated in contributing to Aurora-BIpl1 function. In an attempt to gain a more detailed picture of the budding yeast kinetochore architecture, crosslink-guided in vitro reconstitution revealed novel direct interactions of the inner kinetochore assembled on Cse4CENP-A nucleosomes. The Ame1/Okp1CENP-U/Q heterodimer selectively bound Cse4CENP-A nucleosomes through the Cse4 N-terminus, providing an explanation for the essential role of the COMA complex in budding yeast. Moreover, the Sli15/Ipl1 core chromosomal passenger complex was found to directly interact with COMA in vitro, suggesting a hitherto unknown role of the COMA complex in establishing biorientation. In line with this finding, in vivo artificial tethering of Sli15 to inner kinetochore proteins rescued synthetically lethal subunit deletion phenotypes in a Sli15 centromere targeting deficient mutant. This study reveals characteristics of the inner kinetochore architecture assembled at point centromeres and its implications on chromosomal passenger complex function.

2019-04-12 | PXD011235 | Pride

The COMA complex plays a role in positioning Ipl1 activity proximal to Cse4 nucleosomes

2019-04-12 | PXD011236 | Pride