Condensin in Chromatid Cohesion and Segregation

Uchiyama, Susumu; Fukui, Kiichi

doi:10.1159/000444868

Cited by 5 publications

(5 citation statements)

References 32 publications

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“…7e), a cohesin-associated protein that stabilizes sister chromatids, is probably one of the mechanisms that links TFIP11 depletion with chromosome mis-segregation, as it was also observed upon inhibition of other splicing factors 41 . However, we cannot exclude that the M phase arrest and SSC defect might result from aberrant splicing in multiple mitotic genes such as SMC4 55 or CENPE.…”

Section: Discussionmentioning

confidence: 97%

DHX15-independent roles for TFIP11 in U6 snRNA modification, U4/U6.U5 tri-snRNP assembly and pre-mRNA splicing fidelity

et al. 2021

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The U6 snRNA, the core catalytic component of the spliceosome, is extensively modified post-transcriptionally, with 2’-O-methylation being most common. However, how U6 2’-O-methylation is regulated remains largely unknown. Here we report that TFIP11, the human homolog of the yeast spliceosome disassembly factor Ntr1, localizes to nucleoli and Cajal Bodies and is essential for the 2’-O-methylation of U6. Mechanistically, we demonstrate that TFIP11 knockdown reduces the association of U6 snRNA with fibrillarin and associated snoRNAs, therefore altering U6 2′-O-methylation. We show U6 snRNA hypomethylation is associated with changes in assembly of the U4/U6.U5 tri-snRNP leading to defects in spliceosome assembly and alterations in splicing fidelity. Strikingly, this function of TFIP11 is independent of the RNA helicase DHX15, its known partner in yeast. In sum, our study demonstrates an unrecognized function for TFIP11 in U6 snRNP modification and U4/U6.U5 tri-snRNP assembly, identifying TFIP11 as a critical spliceosome assembly regulator.

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Section: Discussionmentioning

confidence: 97%

DHX15-independent roles for TFIP11 in U6 snRNA modification, U4/U6.U5 tri-snRNP assembly and pre-mRNA splicing fidelity

et al. 2021

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“…1 In meiosis, the generation of mammalian gametes comprises 2 subsequent cell divisions (meiosis I and II) during their development to reduce the ploidy. 9,10 Any errors in these processes generating aneuploidy would lead to the miscarriage, age-related infertility, and high incidence of genetic disorders such as Down syndrome in humans. [14][15][16][17] Meiotic cohesin complexes are composed of 4 essential subunits, including a meiosis-specific Smc1 subunit (Smc1b), 2 additional a-kleisins (Rad21L and Rec8) and another stromal antigen protein (Stag3).…”

Section: Discussionmentioning

confidence: 99%

“…With increasing age, mouse oocytes deficient in the meiosis-specific cohesin Smc1b massively lose SCC and chiasmata. 9,10 Specific inactivation of mouse Smc1b gene at the primordial follicle stage shortly after birth when oocytes had just entered meiosis I dictyate arrest has normal chiasma positions and SCC in the adult, suggesting that Smc1b cohesin needs only be expressed during prophase I before the primordial follicle stage to ensure SCC up to advanced age of mice. 28 Beyond its well-known role in SCC, Smc1b also exerts other functions in various biologic events.…”

Section: Introductionmentioning

confidence: 99%

Smc1β is required for activation of SAC during mouse oocyte meiosis

et al. 2017

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Smc1β is a meiosis-specific cohesin subunit that is essential for sister chromatid cohesion and DNA recombination. Previous studies have shown that Smc1β-deficient mice in both sexes are sterile. Ablation of Smc1β during male meiosis leads to the blockage of spermatogenesis in pachytene stage, and ablation of Smc1β during female meiosis generates a highly error-prone oocyte although it could develop to metaphase II stage. However, the underlying mechanisms regarding how Smc1β maintains the correct meiotic progression in mouse oocytes have not been clearly defined. Here, we find that GFP-fused Smc1β is expressed and localized to the chromosomes from GV to MII stages during mouse oocyte meiotic maturation. Knockdown of Smc1β by microinjection of gene-specific morpholino causes the impaired spindle apparatus and chromosome alignment which are highly correlated with the defective kinetochore-microtubule attachments, consequently resulting in a prominently higher incidence of aneuploid eggs. In addition, the premature extrusion of polar bodies and escape of metaphase I arrest induced by low dose of nocodazole treatment in Smc1β-depleted oocytes indicates that Smc1β is essential for activation of spindle assembly checkpoint (SAC) activity. Collectively, we identify a novel function of Smc1β as a SAC participant beyond its role in chromosome cohesion during mouse oocyte meiosis.

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“…During mitosis, chromosomes have to replicate and the resulting sister chromatids have to segregate in each cell cycle, which generates two genetically identical daughter cells [1, 2]. On the other hand, male and female germ cells both undergo two rounds of meiotic cell divisions (meiosis I and II) during their development in order to reduce the ploidy, and this process generates the formation of haploid gametes, each possessing half the number of chromosomes of the original cells [3, 4]. Errors in meiosis resulting in aneuploidy contribute to miscarriage, the age-related infertility, and the high incidence of genetic disorders such as Down's syndrome in humans [5, 6, 7, 8].…”

Section: Introductionmentioning

confidence: 99%

Stag3 regulates microtubule stability to maintain euploidy during mouse oocyte meiotic maturation

et al. 2016

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Stag3, a meiosis-specific subunit of cohesin complex, has been demonstrated to function in both male and female reproductive systems in mammals. However, its roles during oocyte meiotic maturation have not been fully defined. In the present study, we report that Stag3 uniquely accumulates on the spindle apparatus and colocalizes with microtubule fibers during mouse oocyte meiotic maturation. Depletion of Stag3 by gene-targeting morpholino disrupts normal spindle assembly and chromosome alignment in oocytes. We also find that depletion of Stag3 reduces the acetylated level of tubulin and microtubule resistance to microtubule depolymerizing drug, suggesting that Stag3 is required for microtubule stability. Consistent with these observations, kinetochore-microtubule attachment, an important mechanism controlling chromosome alignment, is severely impaired in Stag3-depleted oocytes, resultantly causing the significantly increased incidence of aneuploid eggs. Collectively, our data reveal that Stag3 is a novel regulator of microtubule dynamics to ensure euploidy during moue oocyte meiotic maturation.

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Condensin in Chromatid Cohesion and Segregation

Cited by 5 publications

References 32 publications

DHX15-independent roles for TFIP11 in U6 snRNA modification, U4/U6.U5 tri-snRNP assembly and pre-mRNA splicing fidelity

DHX15-independent roles for TFIP11 in U6 snRNA modification, U4/U6.U5 tri-snRNP assembly and pre-mRNA splicing fidelity

Smc1β is required for activation of SAC during mouse oocyte meiosis

Stag3 regulates microtubule stability to maintain euploidy during mouse oocyte meiotic maturation

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