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Molecular and Cellular Biology, June 2000, p. 4393-4404, Vol. 20, No. 12
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

DNA Repair Protein Rad55 Is a Terminal Substrate of the DNA Damage Checkpoints

Vladimir I. Bashkirov,1,2,3 Jeff S. King,1,dagger Elena V. Bashkirova,3 Jacqueline Schmuckli-Maurer,1 and Wolf-Dietrich Heyer1,3,4,*

Institute of General Microbiology, CH-3012 Bern, Switzerland1; Institute of Gene Biology, Russian Academy of Sciences, Moscow 117 334, Russia2; and Sections of Microbiology3 and Molecular and Cellular Biology,4 Division of Biological Sciences, University of California, Davis, Davis, California 95616

Received 15 December 1999/Returned for modification 1 March 2000/Accepted 21 March 2000

Checkpoints, which are integral to the cellular response to DNA damage, coordinate transient cell cycle arrest and the induced expression of DNA repair genes after genotoxic stress. DNA repair ensures cellular survival and genomic stability, utilizing a multipathway network. Here we report evidence that the two systems, DNA damage checkpoint control and DNA repair, are directly connected by demonstrating that the Rad55 double-strand break repair protein of the recombinational repair pathway is a terminal substrate of DNA damage and replication block checkpoints. Rad55p was specifically phosphorylated in response to DNA damage induced by the alkylating agent methyl methanesulfonate, dependent on an active DNA damage checkpoint. Rad55p modification was also observed after gamma ray and UV radiation. The rapid time course of phosphorylation and the recombination defects identified in checkpoint-deficient cells are consistent with a role of the DNA damage checkpoint in activating recombinational repair. Rad55p phosphorylation possibly affects the balance between different competing DNA repair pathways.

* Corresponding author. Mailing address: Section of Microbiology, University of California, Davis, One Shields Ave., Davis, CA 95616-8665. Phone: (530) 752-3001. Fax: (530) 752-3011. E-mail: wdheyer{at}ucdavis.edu.

dagger Present address: Rosetta Inpharmatics, Kirkland, WA 98034.

Molecular and Cellular Biology, June 2000, p. 4393-4404, Vol. 20, No. 12
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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