Genetic evidence for a role of Saccharomyces cerevisiae Mph1 in recombinational DNA repair under replicative stress

Yeast
Evandro Rocco PanicoWilfried Kramer

Abstract

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. ...Continue Reading

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Citations

Jun 15, 2012·The Journal of Biological Chemistry·Danielle L DaeeKyungjae Myung
Jun 8, 2011·Journal of Cellular Biochemistry·Robyn L MaherScott W Morrical
Oct 15, 2013·Molecular Cell·Gerard Mazón, Lorraine S Symington
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Aug 10, 2010·Annual Review of Genetics·Wolf-Dietrich HeyerJie Liu
Nov 18, 2010·Journal of Experimental Botany·Alexander Knoll, Holger Puchta
Feb 23, 2020·Genes·Sonia Vidushi Gupta, Kristina Hildegard Schmidt
Feb 20, 2021·Proceedings of the National Academy of Sciences of the United States of America·Nalini DhingraXiaolan Zhao
Mar 12, 2016·Genes & Development·Sonia SilvaMichael Lisby
Sep 6, 2015·Genes & Development·Xiaoyu XueXiaolan Zhao

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