Human DNA polymerase ε is phosphorylated at serine-1940 after DNA damage and interacts with the iron-sulfur complex chaperones CIAO1 and MMS19

DNA Repair (Amst). 2016 Jul:43:9-17. doi: 10.1016/j.dnarep.2016.04.007. Epub 2016 May 7.

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.

Keywords: CIAO1; DNA damage; DNA polymerase epsilon; MMS19.

MeSH terms

  • Alanine / metabolism
  • Amino Acid Substitution
  • Cell Line, Tumor
  • Cell Proliferation
  • Cell Survival
  • DNA / genetics
  • DNA / metabolism*
  • DNA Damage
  • DNA Polymerase II / genetics
  • DNA Polymerase II / metabolism*
  • DNA Repair*
  • HEK293 Cells
  • Humans
  • Iron-Sulfur Proteins / genetics
  • Iron-Sulfur Proteins / metabolism
  • Metallochaperones / genetics
  • Metallochaperones / metabolism*
  • Mutation
  • Osteoblasts / cytology
  • Osteoblasts / metabolism
  • Phosphorylation
  • Poly-ADP-Ribose Binding Proteins
  • Protein Subunits / genetics
  • Protein Subunits / metabolism*
  • Serine / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*

Substances

  • CIAO1 protein, human
  • Iron-Sulfur Proteins
  • MMS19 protein, human
  • Metallochaperones
  • Poly-ADP-Ribose Binding Proteins
  • Protein Subunits
  • Transcription Factors
  • Serine
  • DNA
  • DNA Polymerase II
  • POLE protein, human
  • Alanine