Nucleic Acids Research, 2002, Vol. 30, No. 5 1103-1113
© 2002 Oxford University Press
SGS1 is a multicopy suppressor of srs2: functional overlap between DNA helicases
Department of Physiology, PO Box 147, University of Liverpool, Crown Street, Liverpool L69 3BX, UK
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 srs2
mutant to have a similar genotoxin sensitivity profile and replicative lifespan to the sgs1 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 srs2 and sgs1 mutants was assessed. We report here that SGS1 is a multicopy suppressor of the methyl methanesulphonate (MMS) and hydroxyurea sensitivity of the srs2 mutant, whereas SRS2 overexpression had no complementing ability in the sgs1 mutant. Domains of Sgs1 directly required for processing MMS-induced DNA damage, most notably the helicase domain, are also required for complementation of the srs2 mutant. Although SGS1 overexpression was unable to rescue the shortened mean replicative lifespan of the srs2 mutant, maximum lifespan was significantly increased by multicopy SGS1. We conclude that Sgs1 is able to partially compensate for the loss of Srs2.
* To whom correspondence should be addressed. Tel: +44 151 794 5333; Fax: +44 151 794 5337; Email: amorgan{at}liv.ac.uk
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