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Molecular and Cellular Biology, December 2003, p. 8913-8923, Vol. 23, No. 23
0270-7306/03/$08.00+0     DOI: 10.1128/MCB.23.23.8913-8923.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Yeast Rad52 and Rad51 Recombination Proteins Define a Second Pathway of DNA Damage Assessment in Response to a Single Double-Strand Break

Sang Eun Lee,1,{dagger} Achille Pellicioli,2 Moreshwar B. Vaze,1,{ddagger} Neal Sugawara,1 Anna Malkova,1 Marco Foiani,2 and James E. Haber1*

Rosenstiel Center and Department of Biology, Brandeis University, Waltham, Massachusetts,1 Dipartimento di Genetica e di Biologia dei Microrganismi, Universita' degli Studi di Milano, and Istituto F.I.R.C. di Oncologia Molecolare, 20122 Milan, Italy2

Received 18 September 2002/ Returned for modification 25 November 2002/ Accepted 27 August 2003

Saccharomyces cells with a single unrepaired double-strand break adapt after checkpoint-mediated G2/M arrest. We have found that both Rad51 and Rad52 recombination proteins play key roles in adaptation. Cells lacking Rad51p fail to adapt, but deleting RAD52 suppresses rad51{Delta}. rad52{Delta} also suppresses adaptation defects of srs2{Delta} mutants but not those of yku70{Delta} or tid1{Delta} mutants. Neither rad54{Delta} nor rad55{Delta} affects adaptation. A Rad51 mutant that fails to interact with Rad52p is adaptation defective; conversely, a C-terminal truncation mutant of Rad52p, impaired in interaction with Rad51p, is also adaptation defective. In contrast, rad51-K191A, a mutation that abolishes recombination and results in a protein that does not bind to single-stranded DNA (ssDNA), supports adaptation, as do Rad51 mutants impaired in interaction with Rad54p or Rad55p. An rfa1-t11 mutation in the ssDNA binding complex RPA partially restores adaptation in rad51{Delta} mutants and fully restores adaptation in yku70{Delta} and tid1{Delta} mutants. Surprisingly, although neither rfa1-t11 nor rad52{Delta} mutants are adaptation defective, the rad52{Delta} rfa1-t11 double mutant fails to adapt and exhibits the persistent hyperphosphorylation of the DNA damage checkpoint protein Rad53 after HO induction. We suggest that monitoring of the extent of DNA damage depends on independent binding of RPA and Rad52p to ssDNA, with Rad52p's activity modulated by Rad51p whereas RPA's action depends on Tid1p.

* Corresponding author. Mailing address: MS029 Rosenstiel Center, Brandeis University, Waltham, MA 02454-9110. Phone: (781) 736-2462. Fax: (781) 736-2405. E-mail: haber{at}brandeis.edu.

{dagger} Present address: Department of Molecular Medicine/Institute of Biotechnology, University of Texas Health Science Center—San Antonio, San Antonio, TX 78245.

{ddagger} Present address: Cyclis Pharmaceuticals, Norwood, MA 02062.

Molecular and Cellular Biology, December 2003, p. 8913-8923, Vol. 23, No. 23
0022-538X/03/$08.00+0     DOI: 10.1128/MCB.23.23.8913-8923.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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