49 research outputs found

    A Direct Link between Sister Chromatid Cohesion and Chromosome Condensation Revealed through the Analysis of MCD1 in S. cerevisiae

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    AbstractThe S. cerevisiae MCD1(mitotic chromosome determinant) gene was identified in genetic screens for genes important for chromosome structure. MCD1 is essential for viability and homologs are found from yeast to humans. Analysis of the mcd1 mutant and cell cycle–dependent expression pattern of Mcd1p suggest that this protein functions in chromosome morphogenesis from S phase through mitosis. The mcd1 mutant is defective in sister chromatid cohesion and chromosome condensation. The physical association between Mcd1p and Smc1p, one of the SMC family of chromosomal proteins, further suggests that Mcd1p functions directly on chromosomes. These data implicate Mcd1p as a nexus between cohesion and condensation. We present a model for mitotic chromosome structure that incorporates this previously unsuspected link

    Budding yeast Wpl1p regulates cohesin functions in cohesion, condensation and DNA repair by a common mechanism

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    AbstractCohesin tethers DNA to mediate sister chromatid cohesion, chromosome condensation, and DNA repair. How the cell regulates cohesin to perform these distinct functions remains to be elucidated. One cohesin regulator, Wpl1p, was characterized in the budding yeast,Saccharomyces cerevisiae, as a promoter of cohesion and as an inhibitor of condensation. Here we provide evidence that Wpl1p has an additional function in promoting the timely repair of DNA damage induced during S-phase. In addition to these biological functions, Wpl1p has been implicated as an inhibitor of cohesin’s ability to stably bind DNA by modulating the interface between two subunits (Mcd1p and Smc3p) of the core cohesin complex. We show that Wpl1p likely modulates this interface to regulate all cohesin’s biological functions. Furthermore, we show that Wpl1p regulates cohesion and condensation through the formation of a functional complex with another cohesin-associated factor, Pds5p. In contrast, Wpl1p regulates DNA repair independently of its interaction with Pds5p. Together these results suggest that Wpl1p regulates distinct biological functions of cohesin by Pds5p-dependent and – independent modulation of the Smc3p-Mcd1p interface.</jats:p

    A role for the Smc3 hinge domain in the maintenance of sister chromatid cohesion

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    A screen of cohesin subunit Smc3 reveals that its hinge is a nexus controlling the maintenance of sister chromatid cohesion and condensation. </jats:p

    Cohesin Function in Cohesion, Condensation, and DNA Repair Is Regulated by Wpl1p via a Common Mechanism in <i>Saccharomyces cerevisiae</i>

    No full text
    Abstract Cohesin tethers DNA to mediate sister chromatid cohesion, chromosome condensation, and DNA repair. How the cell regulates cohesin to perform these distinct functions remains to be elucidated. One cohesin regulator, Wpl1p, was characterized in Saccharomyces cerevisiae as a promoter of efficient cohesion and an inhibitor of condensation. Wpl1p is also required for resistance to DNA-damaging agents. Here, we provide evidence that Wpl1p promotes the timely repair of DNA damage induced during S-phase. Previous studies have indicated that Wpl1p destabilizes cohesin’s binding to DNA by modulating the interface between the cohesin subunits Mcd1p and Smc3p. Our results suggest that Wpl1p likely modulates this interface to regulate all of cohesin’s biological functions. Furthermore, we show that Wpl1p regulates cohesion and condensation through the formation of a functional complex with another cohesin-associated factor, Pds5p. In contrast, Wpl1p regulates DNA repair independently of its interaction with Pds5p. Together, these results suggest that Wpl1p regulates distinct biological functions of cohesin by Pds5p-dependent and -independent modulation of the Smc3p/Mcd1p interface.</jats:p
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