Genetic evidence for a role of Saccharomyces cerevisiae Mph1 in recombinational DNA repair under replicative stress.
In yeast as in human, DNA helicases play critical roles in assisting replication fork progression. The Saccharomyces cerevisiae MPH1 gene, homologue of human FANCM, has been involved in homologous recombination and DNA repair. We describe a synthetic growth defect of an mph1 deletion if combined with an srs2 deletion that can result-depending on the genetic background-in synthetic lethality. The lethality is suppressed by mutations in homologous recombination (rad51, rad52, rad55, rad57) and in the DNA damage checkpoint (rad9, rad24, rad17). Importantly, rad54 and mph1, epistatic for damage sensitivity, are subadditive for spontaneous mutator phenotype. Therefore, Mph1 could be placed at the Rad51-mediated strand invasion process, with a function distinct from Rad54. Moreover, siz1 mutation is viable with mph1 and additive for DNA damage sensitivity. mph1 srs2 double mutants, isolated in a background where they are viable, are synergistically sensitive to DNA damage. Moderate overexpression of SGS1 partially suppresses this sensitivity. Finally, we observe an epistatic relationship in terms of sensitivity to camptothecin of mms4 or mus81 to mph1. Overall, our results support a role of Mph1 in assisting replication progression. We propose two models for the resumption of DNA synthesis under replicative stress where Mph1 is placed at the sister chromatid interaction step.
Panico
Evandro Rocco
ER
Department of Molecular Genetics and Preparative Molecular Biology, Institute for Microbiology and Genetics, University of Göttingen, D-37077 Göttingen, Germany. evandropanico@gmail.com
Ede
Christopher
C
Schildmann
Michael
M
Schürer
Kirsten Anke
KA
Kramer
Wilfried
W
D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000378:metabolism*; D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism; D004260:DNA Repair / Q000502:physiology*; D004261:DNA Replication / Q000502:physiology*; D004274:DNA, Recombinant / Q000235:genetics / Q000378:metabolism*; D017353:Gene Deletion; D015966:Gene Expression Regulation, Fungal / Q000502:physiology; D005838:Genotype; D009154:Mutation; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*
D004274:DNA, Recombinant; D029701:Saccharomyces cerevisiae Proteins; C061376:SRS2 protein, S cerevisiae; C491240:MPH1 protein, S cerevisiae; D004265:DNA Helicases; D053487:DEAD-box RNA Helicases