Budding yeast Pds5p regulates sister chromatid cohesion maintenance and is sumoylated to promote cohesion dissolution.
Cristina Aguilar (1), Kristen Stead (1), Christian Davidson (1), Ke Zheng (1), Gary Fortin (1), Pamela Meluh (2), Vincent Guacci (1)
(1) Basic Science, Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA, 19111, USA;
(2) Memorial Sloan-Kettering, Program in Molecular Biology, New York, NY 10021
Sister chromatid cohesion is established during S phase and maintained until anaphase. Pds5p and the cohesin complex (Mcd1p/Scc1p, Smc1p, Smc3p and Scc3p) are required for cohesion and bind to the same chromosomal loci. We have shown Pds5p requires Mcd1p to localize to chromosomes, whereas Mcd1p localization is largely independent of Pds5p, suggesting that Pds5p and cohesin complex play different roles in cohesion. We find that Pds5p is required only for cohesion maintenance, whereas cohesin complex is required for both establishment and maintenance, supporting the idea that Pds5p and cohesin complex play distinct roles. We conducted a high-copy suppressor screen of pds5 mutants and isolated SMT4 (a SUMO isopeptidase) and TOP2. SMT4 and TOP2 suppressed the temperature sensitivity of pds5 mutants, but had no effect on cohesin complex mutants, indicating that suppression is specific for pds5 mutants. We demonstrate that Pds5p is sumoylated and that Smt4p activity regulates Pds5p sumoylation. SMT4 also suppresses the defective cohesion maintenance of pds5 mutants. These data indicate that Smt4p and SUMO play direct roles in modulating cohesion. In contrast, our data indicate that TOP2 suppression does not appear to be directly related to cohesion. We propose a model whereby Pds5p modulates cohesin complex function on chromosomes to maintain cohesion, and that Pds5p sumoylation promotes cohesion dissolution.
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