Disease relevance of MGS1

• 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 [1].

High impact information on MGS1

• Saccharomyces cerevisiae MGS1 is essential in strains deficient in the RAD6-dependent DNA damage tolerance pathway [2].
• Saccharomyces cerevisiae Mgs1 protein, which possesses DNA-dependent ATPase and single strand DNA annealing activities, plays a role in maintaining genomic stability [2].
• The mgs1 mutant is not sensitive to DNA-damaging agents, but the mgs1 rad5 double mutant has increased sensitivity to hydroxyurea and a greatly increased spontaneous mutation rate [2].
• 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 [1].
• Functional and physical interaction of yeast Mgs1 with PCNA: impact on RAD6-dependent DNA damage tolerance [3].

Biological context of MGS1

• The data presented raise the possibility that the absence of MGS1 may impair the processing of Okazaki fragments, leading to genomic instability [4].
• Three other interacting proteins, Mgs1p, Ulp2, and Plp2, participate in chromosome assembling and segregation, whereas the function of two others has not been established [5].
• Characterization of the slow-growth phenotype of S. cerevisiae Whip/Mgs1 Sgs1 double deletion mutants [6].
• Our results suggest that Whip/Mgs1 is implicated in DNA metabolism, and is required for normal growth and cell cycle progression in the absence of Sgs1 [6].
• N1302 contains the consensus sequence for a phosphate-binding loop common to ATP- and GTP-binding proteins and a strictly conserved 'SRC' sequence of unknown function present in all accessory proteins of replicative polymerases [7].

Physical interactions of MGS1

• We also demonstrate that Mgs1 interacts physically with Pol31 in vivo [8].

Regulatory relationships of MGS1

• Surprisingly, deletions of RAD18 and MGS1 aggravated the temperature sensitivity conferred by most ts or cs alleles and specifically suppressed the hys2-1 and hys2-1-like mutations of POL31 [8].
• Mgs1 stimulates the structure-specific nuclease activity of Rad27 (yeast Fen1 or yFen1) in an ATP-dependent manner [4].

Other interactions of MGS1

• Replication fork bypass processes appear to be highly conserved within eukaryotes, with homologs for SGS1 and MGS1 found in both Schizosaccharomyces pombe and mammalian cells [9].
• Moreover, regions I and VII of Pol31, which are specifically sensitive to high levels of Mgs1 and PCNA, could be sites of interaction [8].
• In this study, we identified MGS1 as a multicopy suppressor of the temperature-sensitive dna2Delta405N mutation, a DNA2 allele lacking the N-terminal 405 amino acid residues [4].
• We found that the RFC-like motifs in Whip/Mgs1 are essential for its function [10].

References