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Molecular and Cellular Biology, March 2001, p. 1997-2007, Vol. 21, No. 6
0270-7306/01/$04.00+0 DOI: 10.1128/MCB.21.6.1997-2007.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
Dosage Suppressors of pds1 Implicate
Ubiquitin-Associated Domains in Checkpoint Control
Duncan J.
Clarke,
Guillaume
Mondesert,
Marisa
Segal,
Bonnie
L.
Bertolaet,
Sanne
Jensen,§
Meira
Wolff,
Martha
Henze, and
Steven I.
Reed*
Department of Molecular Biology, The Scripps
Research Institute, La Jolla, California 92037
Received 1 September 2000/Returned for modification 3 October
2000/Accepted 15 December 2000
In budding yeast, anaphase initiation is controlled by
ubiquitin-dependent degradation of Pds1p. Analysis of pds1
mutants implicated Pds1p in the DNA damage, spindle assembly, and
S-phase checkpoints. Though some components of these pathways are
known, others remain to be identified. Moreover, the essential function of Pds1p, independent of its role in checkpoint control, has not been
elucidated. To identify loci that genetically interact with PDS1, we screened for dosage suppressors of a
temperature-sensitive pds1 allele, pds1-128,
defective for checkpoint control at the permissive temperature and
essential for viability at 37°C. Genetic and functional interactions
of two suppressors are described. RAD23 and
DDI1 suppress the temperature and hydroxyurea, but not radiation or nocodazole, sensitivity of pds1-128.
rad23 and ddi1 mutants are partially defective
in S-phase checkpoint control but are proficient in DNA damage and
spindle assembly checkpoints. Therefore, Rad23p and Ddi1p participate
in a subset of Pds1p-dependent cell cycle controls. Both Rad23p and
Ddi1p contain ubiquitin-associated (UBA) domains which are required for
dosage suppression of pds1-128. UBA domains are found in
several proteins involved in ubiquitin-dependent proteolysis, though no
function has been assigned to them. Deletion of the UBA domains of
Rad23p and Ddi1p renders cells defective in S-phase checkpoint control,
implicating UBA domains in checkpoint signaling. Since Pds1p
destruction, and thus checkpoint regulation of mitosis, depends on
ubiquitin-dependent proteolysis, we propose that the UBA domains
functionally interact with the ubiquitin system to control Pds1p
degradation in response to checkpoint activation.
*
Corresponding author. Mailing address: Department of
Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Rd., La Jolla, CA 92037. Phone: (858) 784-9836. Fax: (858) 784-2781. E-mail: sreed{at}scripps.edu.

Present address: Sanofi-Synthelabo, Centre de Recherche de Labege,
31676 Labege,
France.

Present address: Triad Therapeutics, San Diego, CA
92121.
§
Present address: National Institute for Medical Research, Division
of Yeast Genetics, The Ridgeway, Mill Hill, London NW7
1AA, United
Kingdom.
Molecular and Cellular Biology, March 2001, p. 1997-2007, Vol. 21, No. 6
0270-7306/01/$04.00+0 DOI: 10.1128/MCB.21.6.1997-2007.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
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