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Molecular and Cellular Biology, October 2007, p. 6948-6961, Vol. 27, No. 19
0270-7306/07/$08.00+0     doi:10.1128/MCB.00774-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

The Ulp2 SUMO Protease Is Required for Cell Division following Termination of the DNA Damage Checkpoint{triangledown}

David C. Schwartz,1,{dagger} Rachael Felberbaum,2 and Mark Hochstrasser1,2*

Departments of Molecular Biophysics & Biochemistry,1 Molecular, Cell, & Developmental Biology, Yale University, 266 Whitney Avenue, New Haven, Connecticut 06520-81142

Received 2 May 2007/ Returned for modification 15 June 2007/ Accepted 18 July 2007

Eukaryotic genome integrity is maintained via a DNA damage checkpoint that recognizes DNA damage and halts the cell cycle at metaphase, allowing time for repair. Checkpoint signaling is eventually terminated so that the cell cycle can resume. How cells restart cell division following checkpoint termination is poorly understood. Here we show that the SUMO protease Ulp2 is required for resumption of cell division following DNA damage-induced arrest in Saccharomyces cerevisiae, although it is not required for DNA double-strand break repair. The Rad53 branch of the checkpoint pathway generates a signal countered by Ulp2 activity following DNA damage. Interestingly, unlike previously characterized adaptation mutants, ulp2{Delta} mutants do not show persistent Rad53 phosphorylation following DNA damage, suggesting checkpoint signaling has been terminated and no longer asserts an arrest in these cells. Using Cdc14 localization as a cell cycle indicator, we show that nearly half of cells lacking Ulp2 can escape a checkpoint-induced metaphase arrest despite their inability to divide again. Moreover, half of permanently arrested ulp2{Delta} cells show evidence of an aberrant mitotic spindle, suggesting that Ulp2 is required for proper spindle dynamics during cell cycle resumption following a DNA damage-induced cell cycle arrest.


* Corresponding author. Mailing address: Departments of Molecular Biophysics & Biochemistry, Yale University, 266 Whitney Avenue, New Haven, CT 06520-8114. Phone: (203) 432-5101. Fax: (203) 432-5158. E-mail: mark.hochstrasser{at}yale.edu

{triangledown} Published ahead of print on 30 July 2007.

{dagger} Present address: Bureau of Western Hemisphere Affairs, Department of State, 2201 C Street NW, Washington, DC 20520-2810.


Molecular and Cellular Biology, October 2007, p. 6948-6961, Vol. 27, No. 19
0270-7306/07/$08.00+0     doi:10.1128/MCB.00774-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.




This article has been cited by other articles:

  • Kroetz, M. B., Su, D., Hochstrasser, M. (2009). Essential Role of Nuclear Localization for Yeast Ulp2 SUMO Protease Function. Mol. Biol. Cell 20: 2196-2206 [Abstract] [Full Text]  
  • Yeh, E. T. H. (2009). SUMOylation and De-SUMOylation: Wrestling with Life's Processes. J. Biol. Chem. 284: 8223-8227 [Abstract] [Full Text]