The Slx5-Slx8 complex affects sumoylation of DNA repair proteins and negatively regulates recombination Journal Article

   

Authors:	Burgess, R. C.; Rahman, S.; Lisby, M.; Rothstein, R.; Zhao, X.
Article Title:	The Slx5-Slx8 complex affects sumoylation of DNA repair proteins and negatively regulates recombination
Abstract:	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, slx8Δ mutants exhibited clonal lethality, which was due to the overamplification of 2μm, an extrachromosomal plasmid. Interestingly, in both SUMO E2 and slx8Δ 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. Copyright © 2007, American Society for Microbiology. All Rights Reserved.
Keywords:	controlled study; unclassified drug; gene deletion; mutation; dna-binding proteins; nonhuman; dna replication; protein function; protein localization; dna recombination; dna damage; cell cycle s phase; dna repair; gene amplification; dna; regulatory mechanism; saccharomyces cerevisiae; recombination, genetic; multiprotein complexes; saccharomyces cerevisiae proteins; sumo protein; sumoylation; fungal protein; rad51 protein; small ubiquitin-related modifier proteins; rad51 recombinase; rad52 dna repair and recombination protein; protein slx5; protein slx8; rna polymerase i
Journal Title:	Molecular and Cellular Biology
Volume:	27
Issue:	17
ISSN:	0270-7306
Publisher:	American Society for Microbiology
Date Published:	2007-09-01
Start Page:	6153
End Page:	6162
Language:	English
DOI:	10.1128/mcb.00787-07
PUBMED:	17591698
PROVIDER:	scopus
PMCID:	PMC1952148
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-34548213631&partnerID=40&md5=17eed4cd09512d92454608119f040296
Notes:	--- - "Cited By (since 1996): 44" - "Export Date: 17 November 2011" - "CODEN: MCEBD" - "Source: Scopus"

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