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Molecular and Cellular Biology, September 2007, p. 6433-6445, Vol. 27, No. 18
0270-7306/07/$08.00+0     doi:10.1128/MCB.00135-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Phosphorylation of Slx4 by Mec1 and Tel1 Regulates the Single-Strand Annealing Mode of DNA Repair in Budding Yeast{triangledown}

Sonja Flott,1,{dagger} Constance Alabert,2 Geraldine W. Toh,1 Rachel Toth,1 Neal Sugawara,3 David G. Campbell,1 James E. Haber,3 Philippe Pasero,2 and John Rouse1*

MRC Protein Phosphorylation Unit, James Black Centre, University of Dundee, Dundee DD1 5EH, United Kingdom,1 Institute of Human Genetics, CNRS UPR 1142, 141 Rue de la Cardonille, 34396 Montpellier, France,2 Rosenstiel Basic Medical Sciences Research Centre, Waltham, Massachusetts3

Received 22 January 2007/ Returned for modification 1 June 2007/ Accepted 28 June 2007

Budding yeast (Saccharomyces cerevisiae) Slx4 is essential for cell viability in the absence of the Sgs1 helicase and for recovery from DNA damage. Here we report that cells lacking Slx4 have difficulties in completing DNA synthesis during recovery from replisome stalling induced by the DNA alkylating agent methyl methanesulfonate (MMS). Although DNA synthesis restarts during recovery, cells are left with unreplicated gaps in the genome despite an increase in translesion synthesis. In this light, epistasis experiments show that SLX4 interacts with genes involved in error-free bypass of DNA lesions. Slx4 associates physically, in a mutually exclusive manner, with two structure-specific endonucleases, Rad1 and Slx1, but neither of these enzymes is required for Slx4 to promote resistance to MMS. However, Rad1-dependent DNA repair by single-strand annealing (SSA) requires Slx4. Strikingly, phosphorylation of Slx4 by the Mec1 and Tel1 kinases appears to be essential for SSA but not for cell viability in the absence of Sgs1 or for cellular resistance to MMS. These results indicate that Slx4 has multiple functions in responding to DNA damage and that a subset of these are regulated by Mec1/Tel1-dependent phosphorylation.

* Corresponding author. Mailing address: MRC Protein Phosphorylation Unit, James Black Centre, University of Dundee, Dundee DD1 5EH, United Kingdom. Phone: 44-1382-385490. Fax: 44-1382-223778. E-mail: j.rouse{at}dundee.ac.uk

{triangledown} Published ahead of print on 16 July 2007.

{dagger} Present address: Gurdon/CRUK Institute, University of Cambridge, Tennis Court Rd., Cambridge, United Kingdom.

Molecular and Cellular Biology, September 2007, p. 6433-6445, Vol. 27, No. 18
0270-7306/07/$08.00+0     doi:10.1128/MCB.00135-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

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