title: Role of RNA polymerase II carboxy terminal domain phosphorylation in DNA damage response.
abstract: The phosphorylation of C-terminal domain (CTD) of Rpb1p, the largest subunit of RNA polymerase II plays an important role in transcription and the coupling of various cellular events to transcription. In this study, its role in DNA damage response is closely examined in Saccharomyces cerevisiae, focusing specifically on several transcription factors that mediate or respond to the phosphorylation of the CTD. CTDK-1, the pol II CTD kinase, FCP1, the CTD phosphatase, ESS1, the CTD phosphorylation dependent cis-trans isomerase, and RSP5, the phosphorylation dependent pol II ubiquitinating enzyme, were chosen for the study. We determined that the CTD phosphorylation of CTD, which occurred predominantly at serine 2 within a heptapeptide repeat, was enhanced in response to a variety of sources of DNA damage. This modification was shown to be mediated by CTDK-1. Although mutations in ESS1 or FCP1 caused cells to become quite sensitive to DNA damage, the characteristic pattern of CTD phosphorylation remained unaltered, thereby implying that ESS1 and FCP1 play roles downstream of CTD phosphorylation in response to DNA damage. Our data suggest that the location or extent of CTD phosphorylation might be altered in response to DNA damage, and that the modified CTD, ESS1, and FCP1 all contribute to cellular survival in such conditions.
authors.affiliation: College of Pharmacy, Sungkyunkwan University, Suwon, Gyeonggi-do, Republic of Korea.
authors.forename: Su-Jin
authors.initials: SJ
authors.lastname: Jeong
authors.forename: Hye-Jin
authors.initials: HJ
authors.lastname: Kim
authors.forename: Yong-Jin
authors.initials: YJ
authors.lastname: Yang
authors.forename: Ja-Hwan
authors.initials: JH
authors.lastname: Seol
authors.forename: Bo-Young
authors.initials: BY
authors.lastname: Jung
authors.forename: Jeong-Whan
authors.initials: JW
authors.lastname: Han
authors.forename: Hyang-Woo
authors.initials: HW
authors.lastname: Lee
authors.forename: Eun-Jung
authors.initials: EJ
authors.lastname: Cho
mesh_terms: D004249:DNA Damage; D004260:DNA Repair; D015966:Gene Expression Regulation, Fungal; D009154:Mutation; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D019696:Peptidylprolyl Isomerase / Q000235:genetics / Q000502:physiology; D010749:Phosphoprotein Phosphatases / Q000235:genetics / Q000502:physiology; D010766:Phosphorylation; D011494:Protein Kinases / Q000502:physiology; D017434:Protein Structure, Tertiary; D012319:RNA Polymerase II / Q000378:metabolism* / Q000502:physiology*; D012441:Saccharomyces cerevisiae / Q000201:enzymology / Q000502:physiology; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism* / Q000502:physiology*; D014158:Transcription, Genetic
chemical_list: D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D029701:Saccharomyces cerevisiae Proteins; D011494:Protein Kinases; C060137:carboxy-terminal domain kinase; D012319:RNA Polymerase II; D010749:Phosphoprotein Phosphatases; C116022:carboxy-terminal domain phosphatase; C000606845:ESS1 protein, S cerevisiae; D019696:Peptidylprolyl Isomerase