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dc.contributor.authorAlphey, Magnus S.
dc.contributor.authorWolford, Campbell
dc.contributor.authorMacNeill, Stuart
dc.date.accessioned2023-12-20T15:30:01Z
dc.date.available2023-12-20T15:30:01Z
dc.date.issued2023-12-18
dc.identifier.citationAlphey , M S , Wolford , C & MacNeill , S 2023 , ' Canonical binding of Chaetomium thermophilum DNA polymerase δ/ζ subunit PolD3 and flap endonuclease Fen1 to PCNA ' , Frontiers in Molecular Biosciences , vol. 10 , 1320648 . https://doi.org/10.3389/fmolb.2023.1320648en
dc.identifier.issn2296-889X
dc.identifier.otherPURE: 297060201
dc.identifier.otherPURE UUID: 0d0d6e4a-ecb2-4750-8638-9d07e7054318
dc.identifier.otherORCID: /0000-0002-9353-3716/work/149333159
dc.identifier.otherORCID: /0000-0002-0555-0007/work/149333160
dc.identifier.otherScopus: 85182207756
dc.identifier.urihttps://hdl.handle.net/10023/28910
dc.descriptionFunding: This work was funded by the Carnegie Trust for the Universities of Scotland through a Research Incentive Grant (grant reference 70668) and by the School of Biology, University of St Andrews. Article processing charges (APCs) and Open Access charges were covered by the University of St Andrews.en
dc.description.abstractThe sliding clamp PCNA is a key player in eukaryotic genome replication and stability, acting as a platform onto which components of the DNA replication and repair machinery are assembled. Interactions with PCNA are frequently mediated via a short protein sequence motif known as the PCNA-interacting protein (PIP) motif. Here we describe the binding mode of a PIP motif peptide derived from C-terminus of the PolD3 protein from the thermophilic ascomycete fungus C. thermophilum, a subunit of both DNA polymerase δ (Pol δ) and the translesion DNA synthesis polymerase Pol ζ, characterised by isothermal titration calorimetry (ITC) and protein X-ray crystallography. In sharp contrast to the previously determined structure of a Chaetomium thermophilum PolD4 peptide bound to PCNA, binding of the PolD3 peptide is strictly canonical, with the peptide adopting the anticipated 310 helix structure, conserved Gln441 inserting into the so-called Q-pocket on PCNA, and Ile444 and Phe448 forming a two-fork plug that inserts into the hydrophobic surface pocket on PCNA. The binding affinity for the canonical PolD3 PIP-PCNA interaction determined by ITC is broadly similar to that previously determined for the non-canonical PolD4 PIP-PCNA interaction. In addition, we report the structure of a PIP peptide derived from the C. thermophilum Fen1 nuclease bound to PCNA. Like PolD3, Fen1 PIP peptide binding to PCNA is achieved by strictly canonical means. Taken together, these results add to an increasing body of information on how different proteins bind to PCNA, both within and across species.
dc.format.extent9
dc.language.isoeng
dc.relation.ispartofFrontiers in Molecular Biosciencesen
dc.rightsCopyright © 2023 Alphey, Wolford and MacNeill. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.en
dc.subjectPCNAen
dc.subjectPIP motifen
dc.subjectDNA replicationen
dc.subjectDNA polymerase δen
dc.subjectChaetomium thermophilumen
dc.subjectQH426 Geneticsen
dc.subjectDASen
dc.subject.lccQH426en
dc.titleCanonical binding of Chaetomium thermophilum DNA polymerase δ/ζ subunit PolD3 and flap endonuclease Fen1 to PCNAen
dc.typeJournal articleen
dc.contributor.sponsorCarnegie Trusten
dc.description.versionPublisher PDFen
dc.contributor.institutionUniversity of St Andrews. Institute of Behavioural and Neural Sciencesen
dc.contributor.institutionUniversity of St Andrews. Biomedical Sciences Research Complexen
dc.contributor.institutionUniversity of St Andrews. School of Biologyen
dc.identifier.doihttps://doi.org/10.3389/fmolb.2023.1320648
dc.description.statusPeer revieweden
dc.identifier.grantnumber70688en


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