SGS1 is a multicopy suppressor of srs2: functional overlap between DNA helicases

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Abstract
Sgs1 is a member of the RecQ family of DNA helicases, which have been implicated in genomic stability, cancer and ageing. Srs2 is another DNA helicase that shares several phenotypic features with Sgs1 and double sgs1srs2 mutants have a severe synthetic growth phenotype. This suggests that there may be functional overlap between these two DNA helicases. Consistent with this idea, we found the srs2Δ mutant to have a similar genotoxin sensitivity profile and replicative lifespan to the sgs1Δ mutant. In order to directly test if Sgs1 and Srs2 are functionally interchangeable, the ability of high-copy SGS1 and SRS2 plasmids to complement the srs2Δ and sgs1Δ mutants was assessed. We report here that SGS1 is a multicopy suppressor of the methyl methanesulphonate (MMS) and hydroxyurea sensitivity of the srs2Δ mutant, whereas SRS2 overexpression had no complementing ability in the sgs1Δ mutant. Domains of Sgs1 directly required for processing MMS-induced DNA damage, most notably the helicase domain, are also required for complementation of the srs2Δ mutant. Although SGS1 overexpression was unable to rescue the shortened mean replicative lifespan of the srs2Δ mutant, maximum lifespan was significantly increased by multicopy SGS1. We conclude that Sgs1 is able to partially compensate for the loss of Srs2.