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Molecular and Cellular Biology, January 2004, p. 662-674, Vol. 24, No. 2
0270-7306/04/$08.00+0     DOI: 10.1128/MCB.24.2.662-674.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Coordination of DNA Damage Responses via the Smc5/Smc6 Complex

Susan H. Harvey,1,2 Daniel M. Sheedy,1 Andrew R. Cuddihy,1 and Matthew J. O'Connell1,2,3*

Trescowthick Research Laboratories, Peter MacCallum Cancer Centre, Melbourne, Victoria 8006,1 Department of Genetics, University of Melbourne, Parkville, Victoria 3010, Australia,2 Derald H. Ruttenberg Cancer Center, Mount Sinai School of Medicine, New York, New York 100293

Received 20 August 2003/ Returned for modification 19 September 2003/ Accepted 21 October 2003

The detection of DNA damage activates DNA repair pathways and checkpoints to allow time for repair. Ultimately, these responses must be coordinated to ensure that cell cycle progression is halted until repair is completed. Several multiprotein complexes containing members of the structural maintenance of chromosomes family of proteins have been described, including the condensin and cohesin complexes, that are critical for chromosomal organization. Here we show that the Smc5/Smc6 (Smc5/6) complex is required for a coordinated response to DNA damage and normal chromosome integrity. Fission yeast cells lacking functional Smc6 initiate a normal checkpoint response to DNA damage, culminating in the phosphorylation and activation of the Chk1 protein kinase. Despite this, cells enter a lethal mitosis, presumably without completion of DNA repair. Another subunit of the complex, Nse1, is a conserved member of this complex and is also required for this response. We propose that the failure to maintain a checkpoint response stems from the lack of ongoing DNA repair or from defective chromosomal organization, which is the signal to maintain a checkpoint arrest. The Smc5/6 complex is fundamental to genome integrity and may function with the condensin and cohesin complexes in a coordinated manner.

* Corresponding author. Mailing address: Derald H. Ruttenberg Cancer Center, Mount Sinai School of Medicine, One Gustave L. Levy Pl., New York, NY 10029. Phone: (212) 987-5468. Fax: (212) 987-2240. E-mail: matthew.oconnell{at}mssm.edu.

Molecular and Cellular Biology, January 2004, p. 662-674, Vol. 24, No. 2
0022-538X/04/$08.00+0     DOI: 10.1128/MCB.24.2.662-674.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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