Cohesin plays a dual role in gene regulation and sister-chromatid cohesion during meiosis in Saccharomyces cerevisiae.

Department of Biological Science, Florida State University, Tallahassee, Florida 32306-4370, USA.
Genetics (Impact Factor: 4.87). 04/2011; 187(4):1041-51. DOI: 10.1534/genetics.110.122358
Source: PubMed

ABSTRACT Sister-chromatid cohesion mediated by cohesin ensures proper chromosome segregation during cell division. Cohesin is also required for postreplicative DNA double-strand break repair and gene expression. The molecular mechanisms of these diverse cohesin functions remain to be elucidated. Here we report that the cohesin subunits Scc3 and Smc1 are both required for the production of the meiosis-specific subunit Rec8 in the budding yeast Saccharomyces cerevisiae. Using a genetic approach, we depleted Scc3 and Smc1 independently in cells that were undergoing meiosis. Both Scc3- and Smc1-depleted cells were inducible for meiosis, but the REC8 promoter was only marginally activated, leading to reduced levels of REC8 transcription and protein production. In contrast, the expression of MCD1, the mitotic counterpart of REC8, was not subject to Scc3 regulation in vegetative cells. We provide genetic evidence to show that sister-chromatid cohesion is not necessary for activation of REC8 gene expression. Cohesin appears to positively regulate the expression of a variety of genes during yeast meiosis. Our results suggest that the cohesin complex plays a dual role in gene regulation and sister-chromatid cohesion during meiotic differentiation in yeast.

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    ABSTRACT: Faithful segregation of chromosomes during mitosis and meiosis is the cornerstone process of life. Cohesin, a multi-protein complex conserved from yeast to human, plays a crucial role in this process by keeping the sister chromatids together from S-phase to anaphase onset during mitosis and meiosis. Technological advancements have discovered myriad functions of cohesin beyond its role in sister chromatid cohesion, such as transcription regulation, DNA repair, chromosome condensation, homolog pairing, monoorientation of sister kinetochore, etc. Here, we have focused on such functions of cohesin that are either independent of or dependent on its canonical role of sister chromatid cohesion. At the end, human diseases associated with malfunctioning of cohesin, albeit with mostly unperturbed sister chromatid cohesion, have been discussed.
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    ABSTRACT: Human SA/STAG proteins, homologues of the yeast Irr1/Scc3 cohesin, are the least studied constituents of the sister chromatid cohesion complex crucial for proper chromosome segregation. The two SA paralogues, SA1 and SA2, show some specificity towards the chromosome region they stabilize, and SA2, but not SA1, has been shown to participate in transcriptional regulation as well. The molecular basis of this functional divergence is unknown. In silico analysis indicates numerous putative nuclear localization (NLS) and export (NES) signals in the SA proteins, suggesting the possibility of their nucleocytoplasmic shuttling. We studied the functionality of those putative signals by expressing fluorescently tagged SA1 and SA2 in the yeast Saccharomyces cerevisiae. Only the N-terminal NLS turned out to be functional in SA1. In contrast, the SA2 protein has at least two functional NLS and also two functional NES. Depending on the balance between these opposing signals, SA2 resides in the nucleus or is distributed throughout the cell. Validation of the above conclusions in HeLa cells confirmed that the same N-terminal NLS of SA1 is functional in those cells. In contrast, in SA2 the principal NLS functioning in HeLa cells is different from that identified in yeast and is localized to the C-terminus. This is the first demonstration of the possibility of non-nuclear localization of an SA protein. The reported difference in the organization between the two SA homologues may also be relevant to their partially divergent functions. The mechanisms determining subcellular localization of cohesins are only partially conserved between yeast and human cells.
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