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Published online 17 November 2003. doi:10.1083/jcb.200305080
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© The Rockefeller University Press, 0021-9525/2003/11/729 $8.00
The Journal of Cell Biology, Volume 163, Number 4, 729-741

Article

Pds5p regulates the maintenance of sister chromatid cohesion and is sumoylated to promote the dissolution of cohesion



Kristen Stead1, Cristina Aguilar1, Theresa Hartman1, Melissa Drexel1, Pamela Meluh2 and Vincent Guacci1

1 Basic Science Division, Fox Chase Cancer Center, Philadelphia, PA 19111
2 Program in Molecular Biology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021

Address correspondence to Vincent A. Guacci, Fox Chase Cancer Center, Basic Science Division, Room W462, 7701 Burholme Ave., Philadelphia, PA 19111. Tel.: (215) 728-5632. Fax: (215) 728-3616. email: va_guacci{at}fccc.edu

Pds5p and the cohesin complex are required for sister chromatid cohesion and localize to the same chromosomal loci over the same cell cycle window. However, Pds5p and the cohesin complex likely have distinct roles in cohesion. We report that pds5 mutants establish cohesion, but during mitosis exhibit precocious sister dissociation. Thus, unlike the cohesin complex, which is required for cohesion establishment and maintenance, Pds5p is required only for maintenance. We identified SMT4, which encodes a SUMO isopeptidase, as a high copy suppressor of both the temperature sensitivity and precocious sister dissociation of pds5 mutants. In contrast, SMT4 does not suppress temperature sensitivity of cohesin complex mutants. Pds5p is SUMO conjugated, with sumoylation peaking during mitosis. SMT4 overexpression reduces Pds5p sumoylation, whereas smt4 mutants have increased Pds5p sumoylation. smt4 mutants were previously shown to be defective in cohesion maintenance during mitosis. These data provide the first link between a protein required for cohesion, Pds5p, and sumoylation, and suggest that Pds5p sumoylation promotes the dissolution of cohesion.

Key Words: SUMO; cohesin complex; mitosis; centromere; chromosome segregation

K. Stead and C. Aguilar contributed equally to this paper.

Abbreviations used in this paper: CEN, centromere; HU, hydroxyurea; IP, immunoprecipitation; Nz, nocodazole.


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