title: Checkpoint arrest signaling in response to UV damage is independent of nucleotide excision repair in Saccharomyces cerevisiae.
abstract: The recognition of DNA double-stranded breaks or single-stranded DNA gaps as a precondition for cell cycle checkpoint arrest has been well established. However, how bulky base damage such as UV-induced pyrimidine dimers elicits a checkpoint response has remained elusive. Nucleotide excision repair represents the main pathway for UV dimer removal that results in strand interruptions. However, we demonstrate here that Rad53p hyperphosphorylation, an early event of checkpoint signaling in Saccharomyces cerevisiae, is independent of nucleotide excision repair (NER), even if replication as a source of secondary DNA damage is excluded. Thus, our data hint at primary base damage or at UV damage (primary or secondary) that does not need to be processed by NER as the relevant substrate of damage-sensing checkpoint proteins.
authors.affiliation: Department of Radiation Oncology and the Winship Cancer Institute, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
authors.forename: Jena
authors.initials: J
authors.lastname: Taylor
authors.forename: Wolfram
authors.initials: W
authors.lastname: Siede
mesh_terms: D002453:Cell Cycle; D018797:Cell Cycle Proteins; D002469:Cell Separation; D064447:Checkpoint Kinase 2; D004249:DNA Damage; D004260:DNA Repair; D019281:Dimerization; D004307:Dose-Response Relationship, Radiation; D005434:Flow Cytometry; D016193:G1 Phase; D015151:Immunoblotting; D008938:Mitosis; D015739:Nocodazole / Q000494:pharmacology; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins; D015398:Signal Transduction; D013696:Temperature; D013997:Time Factors; D014466:Ultraviolet Rays
chemical_list: D018797:Cell Cycle Proteins; D029701:Saccharomyces cerevisiae Proteins; D064447:Checkpoint Kinase 2; D017346:Protein Serine-Threonine Kinases; C067022:RAD53 protein, S cerevisiae; D015739:Nocodazole