Functional hierarchy of PCNA-interacting motifs in DNA processing enzymes

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Numerous eukaryotic DNA processing enzymes, such as DNA polymerases and ligases, bind the processivity factor PCNA, which acts as a platform to recruit and regulate the binding of enzymes to their DNA substrate. Multiple PCNA-interacting motifs (PIPs) are present in these enzymes, but their individual structural and functional role has been a matter of debate. Recent cryo-EM reconstructions of high-fidelity DNA polymerase Pol δ (Pol δ), translesion synthesis DNA polymerase κ (Pol κ) and Ligase 1 (Lig1) bound to a DNA substrate and PCNA demonstrate that the critical interaction with PCNA involves the internal PIP proximal to the catalytic domain. The ancillary PIPs, located in long disordered regions, are instead invisible in the reconstructions, and appear to function as flexible tethers when the enzymes fall off the DNA. In this review, we discuss the recent structural advancements and propose a functional hierarchy for the PIPs in Pol δ, Pol κ, and Lig1.
Original languageEnglish (US)
StatePublished - Apr 11 2023

Bibliographical note

KAUST Repository Item: Exported on 2023-04-13
Acknowledged KAUST grant number(s): CRG8 URF/1/4036-01-01
Acknowledgements: This work was supported by King Abdullah University of Science and Technology through core funding (to S.M.H. and A.D.B.) and the Competitive Research Award Grant CRG8 URF/1/4036-01-01 (to S.M.H. and A.D.B.).

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)


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