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Biochemistry. 2012 Jan 10;51(1):416-24. doi: 10.1021/bi201638e. Epub 2011 Dec 20.

Phosphorylation of the p68 subunit of Pol δ acts as a molecular switch to regulate its interaction with PCNA.

Author information

1
Department of Biochemistry and Molecular Biology, New York Medical College, Valhalla, New York 10595, United States.

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.

PMID:
22148433
DOI:
10.1021/bi201638e
[Indexed for MEDLINE]

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