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Molecular and Cellular Biology, September 2007, p. 6153-6162, Vol. 27, No. 17
0270-7306/07/$08.00+0     doi:10.1128/MCB.00787-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

The Slx5-Slx8 Complex Affects Sumoylation of DNA Repair Proteins and Negatively Regulates Recombination{triangledown} ,{dagger}

Rebecca C. Burgess,1,{ddagger} Sadia Rahman,2,{ddagger} Michael Lisby,3 Rodney Rothstein,4 and Xiaolan Zhao2*

Department of Biological Sciences, Columbia University, 1212 Amsterdam Avenue, New York, New York 10027,1 Molecular Biology Program, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, New York 10021,2 Department of Molecular Biology, University of Copenhagen, DK-2200 Copenhagen N, Denmark,3 Department of Genetics and Development, Columbia University Medical Center, 701 West 168th Street, New York, New York 10032-27044

Received 3 May 2007/ Returned for modification 29 May 2007/ Accepted 14 June 2007

Recombination is important for repairing DNA lesions, yet it can also lead to genomic rearrangements. This process must be regulated, and recently, sumoylation-mediated mechanisms were found to inhibit Rad51-dependent recombination. Here, we report that the absence of the Slx5-Slx8 complex, a newly identified player in the SUMO (small ubiquitin-like modifier) pathway, led to increased Rad51-dependent and Rad51-independent recombination. The increases were most striking during S phase, suggesting an accumulation of DNA lesions during replication. Consistent with this view, Slx8 protein localized to replication centers. In addition, like SUMO E2 mutants, slx8{Delta} mutants exhibited clonal lethality, which was due to the overamplification of 2µm, an extrachromosomal plasmid. Interestingly, in both SUMO E2 and slx8{Delta} mutants, clonal lethality was rescued by deleting genes required for Rad51-independent recombination but not those involved in Rad51-dependent events. These results suggest that sumoylation negatively regulates Rad51-independent recombination, and indeed, the Slx5-Slx8 complex affected the sumoylation of several enzymes involved in early steps of Rad51-independent recombination. We propose that, during replication, the Slx5-Slx8 complex helps prevent DNA lesions that are acted upon by recombination. In addition, the complex inhibits Rad51-independent recombination via modulating the sumoylation of DNA repair proteins.

* Corresponding author. Mailing address: Molecular Biology Program, Memorial Sloan-Kettering Cancer Center, 1275 York Ave., New York, NY 10021. Phone: (212) 639-5579. Fax: (646) 422-2062. E-mail: zhaox1{at}mskcc.org

{triangledown} Published ahead of print on 25 June 2007.

{dagger} Supplemental material for this article may be found at http://mcb.asm.org/.

{ddagger} R.C.B. and S.R. contributed equally to this work.

Molecular and Cellular Biology, September 2007, p. 6153-6162, Vol. 27, No. 17
0270-7306/07/$08.00+0     doi:10.1128/MCB.00787-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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