Similar Datasets
Project description:To investigate the function of meiosis-specific SMC1beta on chromatin architecture near the telomeric end in primary murine spermatocytes we used a SMC1beta knockout mouse model.
2023-05-04 | GSE230553 | GEO
Project description:To investigate the function of meiosis-specific SMC1beta on chromatin architecture near the telomeric end in primary murine spermatocytes we used a SMC1beta knockout mouse model.
2023-05-04 | GSE230555 | GEO
Project description:To investigate the function of meiosis-specific SMC1beta on chromatin architecture near the telomeric end in primary murine spermatocytes we used a SMC1beta knockout mouse model.
2023-05-04 | GSE230554 | GEO
Project description:Structural maintenance of chromosomes (SMC) proteins fulfill pivotal roles in chromosome dynamics. In yeast, the SMC1-SMC3 heterodimer is required for meiotic sister chromatid cohesion and DNA recombination. Little is known, however, about mammalian SMC proteins in meiotic cells. We have identified a novel SMC protein (SMC1beta), which-except for a unique, basic, DNA binding C-terminal motif-is highly homologous to SMC1 (which may now be called SMC1alpha) and is not present in the yeast genome. SMC1beta is specifically expressed in testes and coimmunoprecipitates with SMC3 from testis nuclear extracts, but not from a variety of somatic cells. This establishes for mammalian cells the concept of cell-type- and tissue-specific SMC protein isoforms. Analysis of testis sections and chromosome spreads of various stages of meiosis revealed localization of SMC1beta along the axial elements of synaptonemal complexes in prophase I. Most SMC1beta dissociates from the chromosome arms in late-pachytene-diplotene cells. However, SMC1beta, but not SMC1alpha, remains chromatin associated at the centromeres up to metaphase II. Thus, SMC1beta and not SMC1alpha is likely involved in maintaining cohesion between sister centromeres until anaphase II.
| S-EPMC99874 | biostudies-literature
Project description:Accurate mitotic chromosome segregation depends on the formation of a microtubule-based bipolar spindle apparatus. We report that the cohesin subunit structural maintenance of chromosomes subunit 1 (SMC1) is recruited to microtubule-bound RNA export factor 1 (Rae1) at the mitotic spindle pole. We locate the Rae1-binding site to a 21-residue-long region, SMC1(947-967) and provide several lines of evidence that phosphorylation of Ser(957) and Ser(966) of SMC1 stimulates binding to Rae1. Imbalances in these assembly pathways caused formation of multipolar spindles. Our data suggest that cohesin's known bundling function for chromatids in mitotic and interphase cells extends to microtubules at the spindle pole.
| S-EPMC2557025 | biostudies-literature
Project description:In humans, meiotic chromosome segregation errors increase dramatically as women age, but the molecular defects responsible are largely unknown. Cohesion along the arms of meiotic sister chromatids provides an evolutionarily conserved mechanism to keep recombinant chromosomes associated until anaphase I. One attractive hypothesis to explain age-dependent nondisjunction (NDJ) is that loss of cohesion over time causes recombinant homologues to dissociate prematurely and segregate randomly during the first meiotic division. Using Drosophila as a model system, we have tested this hypothesis and observe a significant increase in meiosis I NDJ in experimentally aged Drosophila oocytes when the cohesin protein SMC1 is reduced. Our finding that missegregation of recombinant homologues increases with age supports the model that chiasmata are destabilized by gradual loss of cohesion over time. Moreover, the stage at which Drosophila oocytes are most vulnerable to age-related defects is analogous to that at which human oocytes remain arrested for decades. Our data provide the first demonstration in any organism that, when meiotic cohesion begins intact, the aging process can weaken it sufficiently and cause missegregation of recombinant chromosomes. One major advantage of these studies is that we have reduced but not eliminated the SMC1 subunit. Therefore, we have been able to investigate how aging affects normal meiotic cohesion. Our findings that recombinant chromosomes are at highest risk for loss of chiasmata during diplotene argue that human oocytes are most vulnerable to age-induced loss of meiotic cohesion at the stage at which they remain arrested for several years.
| S-EPMC2577922 | biostudies-literature
Project description:The DDK complex is a conserved kinase complex, consisting of a catalytic subunit, Hsk1 (Cdc7), and its regulatory subunit Dfp1 (Dbf4). This kinase is essential for DNA replication. In this work, we show that dfp1-r35, which truncates the Dfp1 C-terminus zinc finger, causes severe meiotic defects, including reduced spore viability, reduced formation of programmed double strand breaks, altered expression of meiotic genes, and disrupted chromosome segregation. There is a high frequency of dyad formation. Mutants are also defective in the phosphorylation and degradation of the meiotic cohesion, Rec8, resulting in a failure to proceed through the MII division. These defects are more pronounced in a haploid meiosis model than in a normal diploid meiosis. Thus, several critical meiotic functions are linked specifically to the C-terminus of Dfp1, which may target specific substrates for phosphorylation by Hsk1.
| S-EPMC3711041 | biostudies-literature
Project description:We identify a new mammalian cohesin subunit, RAD21-like protein (RAD21L), with sequence similarity to RAD21 and REC8. RAD21L localizes along axial elements in early meiotic prophase, in a manner that is spatiotemporally different to either REC8 or RAD21. Remarkably, RAD21L and REC8 have symmetrical, mutually exclusive localization on the not-yet-synapsed homologues, implying that the cohesin patterning could provide a code for homologue recognition. RAD21 transiently localizes to axial elements after the dissociation of RAD21L and REC8 in late pachytene, a period of recombination repair. Further, we show that the removal of cohesins and synaptonemal complex during late meiotic prophase is promoted by Polo-like kinase 1, which is similar to the mitotic prophase pathway.
| S-EPMC3059921 | biostudies-literature
Project description:Mammalian meiocytes feature four meiosis-specific cohesin proteins in addition to ubiquitous ones, but the roles of the individual cohesin complexes are incompletely understood. To decipher the functions of the two meiosis-specific kleisins, REC8 or RAD21L, together with the only meiosis-specific SMC protein SMC1?, we generated Smc1?-/-Rec8-/- and Smc1?-/-Rad21L-/- mouse mutants. Analysis of spermatocyte chromosomes revealed that besides SMC1? complexes, SMC1?/RAD21 and to a small extent SMC1?/REC8 contribute to chromosome axis length. Removal of SMC1? and RAD21L almost completely abolishes all chromosome axes. The sex chromosomes do not pair in single or double mutants, and autosomal synapsis is impaired in all mutants. Super resolution microscopy revealed synapsis-associated SYCP1 aberrantly deposited between sister chromatids and on single chromatids in Smc1?-/-Rad21L-/- cells. All mutants show telomere length reduction and structural disruptions, while wild-type telomeres feature a circular TRF2 structure reminiscent of t-loops. There is no loss of centromeric cohesion in both double mutants at leptonema/early zygonema, indicating that, at least in the mutant backgrounds, an SMC1?/RAD21 complex provides centromeric cohesion at this early stage. Thus, in early prophase I the most prominent roles of the meiosis-specific cohesins are in axis-related features such as axis length, synapsis and telomere integrity rather than centromeric cohesion.
| S-EPMC5085059 | biostudies-literature
Project description:Cohesins are multi-subunit protein complexes that regulate sister chromatid cohesion during mitosis and meiosis. Here we identified a novel kleisin subunit of cohesins, RAD21L, which is conserved among vertebrates. In mice, RAD21L is expressed exclusively in early meiosis: it apparently replaces RAD21 in premeiotic S phase, becomes detectable on the axial elements in leptotene, and stays on the axial/lateral elements until mid pachytene. RAD21L then disappears, and is replaced with RAD21. This behavior of RAD21L is unique and distinct from that of REC8, another meiosis-specific kleisin subunit. Remarkably, the disappearance of RAD21L at mid pachytene correlates with the completion of DNA double-strand break repair and the formation of crossovers as judged by colabeling with molecular markers, ?-H2AX, MSH4, and MLH1. RAD21L associates with SMC3, STAG3, and either SMC1? or SMC1?. Our results suggest that cohesin complexes containing RAD21L may be involved in synapsis initiation and crossover recombination between homologous chromosomes.
| S-EPMC3172173 | biostudies-literature