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.
Copyright © 2016 Elsevier B.V. All rights reserved.
MeSH terms
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Alanine / metabolism
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Amino Acid Substitution
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Cell Line, Tumor
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Cell Proliferation
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Cell Survival
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DNA / genetics
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DNA / metabolism*
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DNA Damage
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DNA Polymerase II / genetics
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DNA Polymerase II / metabolism*
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DNA Repair*
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HEK293 Cells
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Humans
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Iron-Sulfur Proteins / genetics
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Iron-Sulfur Proteins / metabolism
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Metallochaperones / genetics
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Metallochaperones / metabolism*
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Mutation
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Osteoblasts / cytology
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Osteoblasts / metabolism
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Phosphorylation
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Poly-ADP-Ribose Binding Proteins
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Protein Subunits / genetics
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Protein Subunits / metabolism*
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Serine / metabolism
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Transcription Factors / genetics
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Transcription Factors / metabolism*
Substances
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CIAO1 protein, human
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Iron-Sulfur Proteins
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MMS19 protein, human
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Metallochaperones
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Poly-ADP-Ribose Binding Proteins
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Protein Subunits
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Transcription Factors
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Serine
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DNA
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DNA Polymerase II
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POLE protein, human
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Alanine