Srs2 and RecQ homologs cooperate in mei-3-mediated homologous recombination repair of Neurospora crassa.
Homologous recombination and post-replication repair facilitate restart of stalled or collapsed replication forks. The SRS2 gene of Saccharomyces cerevisiae encodes a 3'-5' DNA helicase that functions both in homologous recombination repair and in post-replication repair. This study identifies and characterizes the SRS2 homolog in Neurospora crassa, which we call mus-50. A knockout mutant of N.crassa, mus-50, is sensitive to several DNA-damaging agents and genetic analyses indicate that it is epistatic with mei-3 (RAD51 homolog), mus-11 (RAD52 homolog), mus-48 (RAD55 homolog) and mus-49 (RAD57 homolog), suggesting a role for mus-50 in homologous recombination repair. However, epistasis evidence has presented that MUS50 does not participate in post-replication repair in N.crassa. Also, the N.crassa mus-25 (RAD54 homolog) mus-50 double mutant is viable, which is in contrast to the lethal phenotype of the equivalent rad54 srs2 mutant in S.cerevisiae. Tetrad analysis revealed that mus-50 in combination with mutations in two RecQ homologs, qde-3 and recQ2, is lethal, and this lethality is suppressed by mutation in mei-3, mus-11 or mus-25. Evidence is also presented for the two independent pathways for recovery from camptothecin-induced replication fork arrest: one pathway is dependent on QDE3 and MUS50 and the other pathway is dependent on MUS25 and RECQ2.
Suzuki
Keiichiro
K
Department of Regulation-Biology, Faculty of Science, Saitama University Shimo-okubo 255, Sakura-ku, Saitama City 338-8570, Japan.
Kato
Akihiro
A
Sakuraba
Yoshiyuki
Y
Inoue
Hirokazu
H
D004265:DNA Helicases / Q000235:genetics / Q000502:physiology*; D004260:DNA Repair; D004843:Epistasis, Genetic; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D005804:Genes, Lethal; D008741:Methyl Methanesulfonate / Q000633:toxicity; D009154:Mutation; D009492:Neurospora crassa / Q000187:drug effects / Q000201:enzymology / Q000235:genetics*; D011995:Recombination, Genetic; D013489:Suppression, Genetic
D005656:Fungal Proteins; C083569:MEI-3 protein, Neurospora crassa; D008741:Methyl Methanesulfonate; D004265:DNA Helicases; C402647:QDE-3 protein, Neurospora crassa