Sumoylation of the BLM ortholog, Sgs1, promotes telomere-telomere recombination in budding yeast.
BLM and WRN are members of the RecQ family of DNA helicases, and in humans their loss is associated with syndromes characterized by genome instability and cancer predisposition. As the only RecQ DNA helicase in the yeast Saccharomyces cerevisiae, Sgs1 is known to safeguard genome integrity through its role in DNA recombination. Interestingly, WRN, BLM and Sgs1 are all known to be modified by the small ubiquitin-related modifier (SUMO), although the significance of this posttranslational modification remains elusive. Here, we demonstrate that Sgs1 is specifically sumoylated under the stress of DNA double strand breaks. The major SUMO attachment site in Sgs1 is lysine 621, which lies between the Top3 binding domain and the DNA helicase domain. Surprisingly, sumoylation of K621 was found to be uniquely required for Sgs1's role in telomere-telomere recombination. In contrast, sumoylation was dispensable for Sgs1's roles in DNA damage tolerance, supppression of direct repeat and rDNA recombination, and promotion of top3Delta slow growth. Our results demonstrate that although modification by SUMO is a conserved feature of RecQ family DNA helicases, the major sites of modification are located on different domains of the protein in different organisms. We suggest that sumoylation of different domains of RecQ DNA helicases from different organisms contributes to conserved roles in regulating telomeric recombination.
Lu
Chia-Yin
CY
Department of Microbiology, College of Medicine, National Taiwan University, Taipei, Taiwan.
Tsai
Cheng-Hui
CH
Brill
Steven J
SJ
Teng
Shu-Chun
SC
D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair; D004275:DNA, Ribosomal / Q000737:chemistry; D008239:Lysine / Q000378:metabolism; D053484:RecQ Helicases / Q000737:chemistry / Q000378:metabolism*; D011995:Recombination, Genetic; D012441:Saccharomyces cerevisiae / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000378:metabolism*; D025841:Small Ubiquitin-Related Modifier Proteins / Q000378:metabolism*; D016615:Telomere / Q000737:chemistry*
D004275:DNA, Ribosomal; D029701:Saccharomyces cerevisiae Proteins; D025841:Small Ubiquitin-Related Modifier Proteins; C090472:SGS1 protein, S cerevisiae; D053484:RecQ Helicases; D008239:Lysine