title: Human DNA polymerase ε is phosphorylated at serine-1940 after DNA damage and interacts with the iron-sulfur complex chaperones CIAO1 and MMS19.
abstract: We describe a dynamic phosphorylation on serine-1940 of the catalytic subunit of human Pol ε, POLE1, following DNA damage. We also describe novel interactions between POLE1 and the iron-sulfur cluster assembly complex CIA proteins CIAO1 and MMS19. We show that serine-1940 is essential for the interaction between POLE1 and MMS19, but not POLE1 and CIAO1. No defect in either proliferation or survival was identified when POLE1 serine-1940 was mutated to alanine in human cells, even following treatment with DNA damaging agents. We conclude that serine-1940 phosphorylation and the interaction between serine-1940 and MMS19 are not essential functions in the C terminal domain of the catalytic subunit of DNA polymerase ε.
authors.affiliation: Department of Radiation Oncology, University of Pittsburgh School of Medicine, Hillman Cancer Center, Research Pavilion, Suite 2.6, 5117 Centre Avenue, Pittsburgh, PA 15213-1863, USA.
authors.forename: Tatiana N
authors.initials: TN
authors.lastname: Moiseeva
authors.affiliation: Department of Radiation Oncology, University of Pittsburgh School of Medicine, Hillman Cancer Center, Research Pavilion, Suite 2.6, 5117 Centre Avenue, Pittsburgh, PA 15213-1863, USA; Department of Oncology, University of Alberta, Cross Cancer Institute, 11560 University Avenue, Edmonton, AB T6 G 1Z2, Canada.
authors.forename: Armin M
authors.initials: AM
authors.lastname: Gamper
authors.affiliation: Women's Health Integrated Research Center at Inova Health System, Department of Defense Gynecologic Cancer Center of Excellence, Annandale, VA 22003, USA.
authors.forename: Brian L
authors.initials: BL
authors.lastname: Hood
authors.affiliation: Women's Health Integrated Research Center at Inova Health System, Department of Defense Gynecologic Cancer Center of Excellence, Annandale, VA 22003, USA.
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Conrads
authors.affiliation: Department of Radiation Oncology, University of Pittsburgh School of Medicine, Hillman Cancer Center, Research Pavilion, Suite 2.6, 5117 Centre Avenue, Pittsburgh, PA 15213-1863, USA; Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Hillman Cancer Center, Research Pavilion, Suite 2.6, 5117 Centre Avenue, Pittsburgh, PA 15213-1863, USA. Electronic address: bakkenistcj@upmc.edu.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Bakkenist
mesh_terms: D000409:Alanine / Q000378:metabolism; D019943:Amino Acid Substitution; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D004247:DNA / Q000235:genetics / Q000378:metabolism*; D004249:DNA Damage; D004257:DNA Polymerase II / Q000235:genetics / Q000378:metabolism*; D004260:DNA Repair; D057809:HEK293 Cells; D006801:Humans; D007506:Iron-Sulfur Proteins / Q000235:genetics / Q000378:metabolism; D056511:Metallochaperones / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism; D010766:Phosphorylation; D000075223:Poly-ADP-Ribose Binding Proteins; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism*; D012694:Serine / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: C112111:CIAO1 protein, human; D007506:Iron-Sulfur Proteins; C416322:MMS19 protein, human; D056511:Metallochaperones; D000075223:Poly-ADP-Ribose Binding Proteins; D021122:Protein Subunits; D014157:Transcription Factors; D012694:Serine; D004247:DNA; D004257:DNA Polymerase II; C119525:POLE protein, human; D000409:Alanine
keywords: CIAO1; DNA damage; DNA polymerase epsilon; MMS19