title: A postsynaptic role for Rhp55/57 that is responsible for cell death in Deltarqh1 mutants following replication arrest in Schizosaccharomyces pombe.
abstract: Following replication arrest, multiple cellular responses are triggered to maintain genomic integrity. In fission yeast, the RecQ helicase, Rqh1, plays a critical role in this process. This is demonstrated in Deltarqh1 cells that, following treatment with hydroxyurea (HU), undergo an aberrant mitosis leading to cell death. Previous data suggest that Rqh1 functions with homologous recombination (HR) in recovery from replication arrest. We have found that loss of the HR genes rhp55(+) or rhp57(+), but not rhp51(+) or rhp54(+), suppresses the HU sensitivity of Deltarqh1 cells. Much of this suppression requires Rhp51 and Rhp54. In addition, this suppression is partially dependent on swi5(+). In budding yeast, overexpressing Rad51 (the Rhp51 homolog) minimized the need for Rad55/57 (Rhp55/57) in nucleoprotein filament formation. We overexpressed Rhp51 in Schizosaccharomyces pombe and found that it greatly reduced the requirement for Rhp55/57 in recovery from DNA damage. However, overexpressing Rhp51 did not change the Deltarhp55 suppression of the HU sensitivity of Deltarqh1, supporting an Rhp55/57 function during HR independent of nucleoprotein filament formation. These results are consistent with Rqh1 playing a role late in HR following replication arrest and provide evidence for a postsynaptic function for Rhp55/57.
authors.affiliation: Graduate Program in Anatomy and Cell Biology, Department of Anatomy and Cell Biology, Columbia University, New York, NY 10032, USA.
authors.forename: Justin C
authors.initials: JC
authors.lastname: Hope
authors.forename: Mohamed
authors.initials: M
authors.lastname: Maftahi
authors.forename: Greg A
authors.initials: GA
authors.lastname: Freyer
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism / Q000502:physiology*; D016923:Cell Death; D004249:DNA Damage; D004265:DNA Helicases / Q000235:genetics* / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D016521:Electrophoresis, Gel, Pulsed-Field; D005816:Genetic Complementation Test; D005838:Genotype; D006918:Hydroxyurea / Q000494:pharmacology; D008938:Mitosis; D008957:Models, Genetic; D009154:Mutation; D009698:Nucleoproteins / Q000737:chemistry; D010957:Plasmids / Q000378:metabolism; D011995:Recombination, Genetic; D012568:Schizosaccharomyces / Q000235:genetics* / Q000502:physiology; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D012680:Sensitivity and Specificity; D013569:Synapses; D013997:Time Factors
chemical_list: D004268:DNA-Binding Proteins; D009698:Nucleoproteins; C121634:RHP55 protein, S pombe; D029702:Schizosaccharomyces pombe Proteins; D000251:Adenosine Triphosphatases; C442472:Rhp57 protein, S pombe; D004265:DNA Helicases; C106462:Rqh1 protein, S pombe; D006918:Hydroxyurea