RAD53, DUN1 and PDS1 define two parallel G2/M checkpoint pathways in budding yeast.
Eukaryotic checkpoint genes regulate multiple cellular responses to DNA damage. In this report, we examine the roles of budding yeast genes involved in G2/M arrest and tolerance to UV exposure. A current model posits three gene classes: those encoding proteins acting on damaged DNA (e.g. RAD9 and RAD24), those transducing a signal (MEC1, RAD53 and DUN1) or those participating more directly in arrest (PDS1). Here, we define important features of the pathways subserved by those genes. MEC1, which we find is required for both establishment and maintenance of G2/M arrest, mediates this arrest through two parallel pathways. One pathway requires RAD53 and DUN1 (the 'RAD53 pathway'); the other pathway requires PDS1. Each pathway independently contributes approximately 50% to G2/M arrest, effects demonstrable after cdc13-induced damage or a double-stranded break inflicted by the HO endonuclease. Similarly, both pathways contribute independently to tolerance of UV irradiation. How the parallel pathways might interact ultimately to achieve arrest is not yet understood, but we do provide evidence that neither the RAD53 nor the PDS1 pathway appears to maintain arrest by inhibiting adaptation. Instead, we think it likely that both pathways contribute to establishing and maintaining arrest.
Gardner
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Department of Molecular and Cellular Biology, The University of Arizona, PO Box 21016, Tucson, AZ 85721-0106, USA.
Putnam
C W
CW
Weinert
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D000483:Alleles; D002453:Cell Cycle / Q000235:genetics / Q000528:radiation effects; D018797:Cell Cycle Proteins / Q000235:genetics / Q000502:physiology; D064447:Checkpoint Kinase 2; D019926:Cyclin B / Q000235:genetics / Q000502:physiology; D004249:DNA Damage / Q000528:radiation effects; D015252:Deoxyribonucleases, Type II Site-Specific / Q000235:genetics / Q000378:metabolism; D004843:Epistasis, Genetic; D005656:Fungal Proteins / Q000235:genetics / Q000502:physiology*; D005800:Genes, Fungal / Q000235:genetics / Q000502:physiology; D018816:Genes, cdc / Q000235:genetics / Q000502:physiology; D047908:Intracellular Signaling Peptides and Proteins; D008938:Mitosis / Q000528:radiation effects; D008954:Models, Biological; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology*; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases; D012441:Saccharomyces cerevisiae / Q000166:cytology* / Q000235:genetics / Q000502:physiology / Q000528:radiation effects; D029701:Saccharomyces cerevisiae Proteins; D064249:Securin; D013696:Temperature; D014466:Ultraviolet Rays
D018797:Cell Cycle Proteins; D019926:Cyclin B; D005656:Fungal Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; C578004:PDS1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D064249:Securin; C069930:rad9 protein; D011494:Protein Kinases; C104169:DUN1 protein, S cerevisiae; D064447:Checkpoint Kinase 2; C088937:MEC1 protein, S cerevisiae; D017346:Protein Serine-Threonine Kinases; C067022:RAD53 protein, S cerevisiae; C530845:HO protein, S cerevisiae; C037725:SCEI protein, S cerevisiae; D015252:Deoxyribonucleases, Type II Site-Specific