title: Phosphorylation of the p68 subunit of Pol δ acts as a molecular switch to regulate its interaction with PCNA.
abstract: DNA polymerase delta (Pol δ) is a central enzyme for eukaryotic DNA replication and repair. Pol δ is a complex of four subunits p125, p68, p50, and p12. The functional properties of Pol δ are largely determined by its interaction with its DNA sliding clamp PCNA (proliferating cellular nuclear antigen). The regulatory mechanisms that govern the association of Pol δ with PCNA are largely unknown. In this study, we identified S458, located in the PCNA-interacting protein (PIP-Box) motif of p68, as a phosphorylation site for PKA. Phosphomimetic mutation of S458 resulted in a decrease in p68 affinity for PCNA as well as the processivity of Pol δ. Our results suggest a role of phosphorylation of the PIP-motif of p68 as a molecular switch that dynamically regulates the functional properties of Pol δ.
authors.affiliation: Department of Biochemistry and Molecular Biology, New York Medical College, Valhalla, New York 10595, United States.
authors.forename: Amal A
authors.initials: AA
authors.lastname: Rahmeh
authors.forename: Yajing
authors.initials: Y
authors.lastname: Zhou
authors.forename: Bin
authors.initials: B
authors.lastname: Xie
authors.forename: Hao
authors.initials: H
authors.lastname: Li
authors.forename: Ernest Y C
authors.initials: EY
authors.lastname: Lee
authors.forename: Marietta Y W T
authors.initials: MY
authors.lastname: Lee
mesh_terms: D020816:Amino Acid Motifs / Q000235:genetics; D000595:Amino Acid Sequence; D001224:Aspartic Acid / Q000235:genetics; D017868:Cyclic AMP-Dependent Protein Kinases / Q000737:chemistry / Q000502:physiology; D004258:DNA Polymerase III / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000235:genetics; D015536:Down-Regulation / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D018716:Molecular Mimicry / Q000235:genetics; D008969:Molecular Sequence Data; D009154:Mutation; D010766:Phosphorylation / Q000235:genetics; D018809:Proliferating Cell Nuclear Antigen / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding / Q000235:genetics; D011499:Protein Processing, Post-Translational / Q000235:genetics; D021122:Protein Subunits / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics; D012694:Serine / Q000235:genetics
chemical_list: D018809:Proliferating Cell Nuclear Antigen; D021122:Protein Subunits; D001224:Aspartic Acid; D012694:Serine; D017868:Cyclic AMP-Dependent Protein Kinases; D004258:DNA Polymerase III