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The Proliferating Cell Nuclear Antigen (PCNA)-interacting Protein (PIP) Motif of DNA Polymerase η Mediates Its Interaction with the C-terminal Domain of Rev1
Journal article   Open access   Peer reviewed

The Proliferating Cell Nuclear Antigen (PCNA)-interacting Protein (PIP) Motif of DNA Polymerase η Mediates Its Interaction with the C-terminal Domain of Rev1

Elizabeth M Boehm, Kyle T Powers, Christine M Kondratick, Maria Spies, Jon C D Houtman and M Todd Washington
The Journal of biological chemistry, Vol.291(16), pp.8735-8744
04/15/2016
DOI: 10.1074/jbc.M115.697938
PMCID: PMC4861442
PMID: 26903512
url
https://doi.org/10.1074/jbc.M115.697938View
Published (Version of record) Open Access

Abstract

Y-family DNA polymerases, such as polymerase η, polymerase ι, and polymerase κ, catalyze the bypass of DNA damage during translesion synthesis. These enzymes are recruited to sites of DNA damage by interacting with the essential replication accessory protein proliferating cell nuclear antigen (PCNA) and the scaffold protein Rev1. In most Y-family polymerases, these interactions are mediated by one or more conserved PCNA-interacting protein (PIP) motifs that bind in a hydrophobic pocket on the front side of PCNA as well as by conserved Rev1-interacting region (RIR) motifs that bind in a hydrophobic pocket on the C-terminal domain of Rev1. Yeast polymerase η, a prototypical translesion synthesis polymerase, binds both PCNA and Rev1. It possesses a single PIP motif but not an RIR motif. Here we show that the PIP motif of yeast polymerase η mediates its interactions both with PCNA and with Rev1. Moreover, the PIP motif of polymerase η binds in the hydrophobic pocket on the Rev1 C-terminal domain. We also show that the RIR motif of human polymerase κ and the PIP motif of yeast Msh6 bind both PCNA and Rev1. Overall, these findings demonstrate that PIP motifs and RIR motifs have overlapping specificities and can interact with both PCNA and Rev1 in structurally similar ways. These findings also suggest that PIP motifs are a more versatile protein interaction motif than previously believed.
 Protein Structure, Tertiary Saccharomyces cerevisiae - genetics Humans Nuclear Proteins - metabolism Saccharomyces cerevisiae Proteins - genetics DNA-Binding Proteins - genetics DNA-Directed DNA Polymerase - genetics Amino Acid Motifs DNA-Binding Proteins - metabolism Saccharomyces cerevisiae - metabolism Proliferating Cell Nuclear Antigen - genetics Saccharomyces cerevisiae Proteins - metabolism Nucleotidyltransferases - genetics Protein Binding DNA-Directed DNA Polymerase - metabolism Nucleotidyltransferases - metabolism Nuclear Proteins - genetics Proliferating Cell Nuclear Antigen - metabolism

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