SGS1 , a
helicase and yeast homolog of BLM and WRN , was identified
as a mutation that suppressed the slow growth of top3 mutants.
SGS1 null mutants display elevated rDNA recombination and
premature aging, but are relatively healthy. We conducted a synthetic
lethal screen with SGS1 , reasoning that interacting genes should
share essential functions with SGS1 . Thirty-one synthetic lethal
strains were identified and placed into six complementation groups. Five
of the six cloned genes ( SLX1-6 ) correspond to novel ORFs of
unknown function. SLX1 and SLX3 have homologs in one or
more organisms: C. elegans , S. pombe and H.
sapiens . Null mutants of SLX1-4 have been constructed and no
growth defects have been detected in the single mutants. However, each
slx null is lethal in combination with top3 , and
slx2 and slx3 interact genetically with top1 ,
suggesting that the SLX proteins function in controlling DNA structure.
Phenotypic and genetic analyses of these mutants will be presented, as
well as terminal phenotypes for sgs1 slx double mutants. The
requirement for SGS1 in slx strains provides a unique
assay for SGS1 activity, and we have conducted a structure function
analysis of SGS1 using this method. We find that, in all slx
mutants, both DNA helicase activity and the N-terminus are required for
viability. However, some C-terminal truncations are tolerated. Our
results suggest that SGS1 contains at least two functional domains in
addition to the helicase domain.
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