Role of cleavage by separase of the Rec8 kleisin subunit of cohesin during mammalian meiosis I

Kudo, Norio; Anger, Martin; Peters, Antoine H.F.M.; Stemmann, Olaf; Theussl, Hans-Christian; Helmhart, Wolfgang; Kudo, Hiromi; Heyting, C.; Nasmyth, Kim

doi:10.1242/jcs.035287

Cited by 98 publications

(107 citation statements)

References 51 publications

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“…Although abnormal spermatids with a 4C DNA content are known to be generated by the inhibition of caspaseinduced Rec8 cleavage (Kudo et al, 2009), incomplete release of cohesin in TH2A/TH2B-deficient spermatocytes did not result in the accumulation of abnormal spermatids with a 4C DNA content. Recently, Montellier et al (2013) reported that mutant mice lacking TH2B expression exhibit no defect during spermiogenesis, indicating that a loss of TH2B alone is not sufficient to disturb histone replacement.…”

Section: Introductionmentioning

confidence: 85%

Disruption ofTh2aandTh2bgenes causes defects in spermatogenesis

et al. 2015

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The variant histones TH2A and TH2B are abundant in the testis, but their roles in spermatogenesis remain elusive. Here, we show that male mutant mice lacking both Th2a and Th2b genes were sterile, with few sperm in the epididymis. In the mutant testis, the lack of TH2B was compensated for by overexpression of H2B, whereas overexpression of H2A was not observed, indicating a decrease in the total histone level. Mutant mice exhibited two defects: incomplete release of cohesin at interkinesis after meiosis I and histone replacement during spermiogenesis. In the mutant testis, secondary spermatocytes at interkinesis accumulated and cohesin was not released normally, suggesting that the retained cohesion of sister chromatids delayed the subsequent entry into meiosis II. In addition, impaired chromatin incorporation of TNP2 and degenerated spermatids were observed in the mutant testis. These results suggest that a loss of TH2A and TH2B function in chromatin dynamics or a decrease in the total histone levels causes defects in both cohesin release and histone replacement during spermatogenesis.

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Section: Introductionmentioning

confidence: 85%

Disruption ofTh2aandTh2bgenes causes defects in spermatogenesis

et al. 2015

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“…The first involves negative phosphorylation by Cdk1 and the second involves binding to a chaperone protein called securin (initially called PTTG in human cells) (Shindo et al, 2012). During exit from both MI and at fertilization in MII, separase needs to be activated (Kudo et al, 2006;Kudo et al, 2009). This is triggered directly by a loss of securin and indirectly via a loss of cyclin B1, both of which are effected by the anaphasepromoting complex/cyclosome (APC), as discussed below.…”

Section: The Roles Of Cdk1 and Separase In Meiosismentioning

confidence: 99%

Molecular causes of aneuploidy in mammalian eggs

2013

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SummaryMammalian oocytes are particularly error prone in segregating their chromosomes during their two meiotic divisions. This results in the creation of an embryo that has inherited the wrong number of chromosomes: it is aneuploid. The incidence of aneuploidy rises significantly with maternal age and so there is much interest in understanding this association and the underlying causes of aneuploidy. The spindle assembly checkpoint, a surveillance mechanism that operates in all cells to prevent chromosome mis-segregation, and the cohesive ties that hold those chromosomes together, have thus both been the subject of intensive investigation in oocytes. It is possible that a lowered sensitivity of the spindle assembly checkpoint to certain types of chromosome attachment error may endow oocytes with an innate susceptibility to aneuploidy, which is made worse by an age-related loss in the factors that hold the chromosomes together.

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“…22,24,25 In addition to the regulation of gene expression, cohesin has also other important functions: it forms a huge tripartite ring, mediates the sister chromatid cohesion, and facilitates the repair of damaged DNA. 26,27 From our analysis, we can postulate that HLA-DQA1 and HLA-DRB1 may represent a genetic biomarker for predicting differences in ID conditions, but also that polymorphisms or mutations of the cohesin subunits might have an important role for the non-disjunction of the chromosomes 21 and/or for the dysregulation of the expression of many genes.…”

Section: Gene Expression and Iq In Trisomy 21mentioning

confidence: 92%

The intellectual disability of trisomy 21: differences in gene expression in a case series of patients with lower and higher IQ

Mégarbané

Noguier²,

Stora

et al. 2013

Eur J Hum Genet

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Trisomy 21 (T21), or Down syndrome (DS), is the most frequent and recognizable cause of intellectual disabilities. The level of disability, as evaluated by the intelligence quotient (IQ) test, varies considerably between patients independent of other factors. To determine the genetic or molecular basis of this difference, a high throughput transcriptomic analysis was performed on twenty T21 patients with high and low IQ, and 10 healthy controls using Digital Gene Expression. More than 90 millions of tags were sequenced in the three libraries. A total of 80 genes of potential interest were selected for the qPCR experiment validation, and three housekeeping genes were used for normalizing purposes. HLA DQA1 and HLA DRB1 were significantly downregulated among the patients with a low IQ, the values found in the healthy controls being intermediate between those noted in the IQ þ and IQ À T21 patients. Interestingly, the intergenic region between these genes contains a binding sequence for the CCCTC-binding factor, or CTCF, and cohesin (a multisubunit complex), both of which are essential for expression of HLA DQA1 and HLA DRB1 and numerous other genes. Our results might lead to the discovery of genes, or genetic markers, that are directly involved in several phenotypes of DS and, eventually, to the identification of potential targets for therapeutic interventions.

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Role of cleavage by separase of the Rec8 kleisin subunit of cohesin during mammalian meiosis I

Abstract: SummaryRole of cleavage by separase of the Rec8 kleisin subunit of cohesin during mammalian meiosis I

Cited by 98 publications

References 51 publications

Disruption ofTh2aandTh2bgenes causes defects in spermatogenesis

Disruption ofTh2aandTh2bgenes causes defects in spermatogenesis

Molecular causes of aneuploidy in mammalian eggs

The intellectual disability of trisomy 21: differences in gene expression in a case series of patients with lower and higher IQ

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