Changes in
DNA superhelicity during DNA replication are mediated primarily by the activities of
DNA helicases and topoisomerases. If these activities are defective, the progression of the replication fork can be hindered or blocked, which can lead to double-strand breaks, elevated recombination in regions of repeated
DNA, and
genome instability.
Hereditary diseases like Werner's and
Bloom's Syndromes are caused by defects in
DNA helicases, and these diseases are associated with
genome instability and
carcinogenesis in humans. Here we report a Saccharomyces cerevisiae gene, MGS1 (Maintenance of
Genome Stability 1), which encodes a
protein belonging to the AAA(+) class of
ATPases, and whose central region is similar to Escherichia coli RuvB, a
Holliday junction branch migration motor
protein. The Mgs1 orthologues are highly conserved in prokaryotes and eukaryotes. The Mgs1
protein possesses
DNA-dependent ATPase and single-strand
DNA annealing activities. An mgs1 deletion mutant has an elevated rate of mitotic recombination, which causes
genome instability. The mgs1 mutation is synergistic with a mutation in top3 (encoding
topoisomerase III), and the double mutant exhibits severe growth defects and markedly increased
genome instability. In contrast to the mgs1 mutation, a mutation in the sgs1 gene encoding
a DNA helicase homologous to the Werner and Bloom helicases suppresses both the growth defect and the increased
genome instability of the top3 mutant. Therefore, evolutionarily conserved Mgs1 may play a role together with RecQ family helicases and
DNA topoisomerases in maintaining proper
DNA topology, which is essential for
genome stability.