Structural basis for the increased processivity of D- family DNA polymerases in complex with PCNA
Type | Article | ||||||||||||||||||||||||||||||||||||
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Date | 2020-03 | ||||||||||||||||||||||||||||||||||||
Language | English | ||||||||||||||||||||||||||||||||||||
Author(s) | Madru Clément1, Henneke Ghislaine![]() |
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Affiliation(s) | 1 : Unit of Structural Dynamics of Macromolecules, Institut Pasteur and CNRS UMR 3528, Paris, France 2 : CNRS, Ifremer, Université de Brest, Laboratoire de Microbiologie des Environnements Extrêmes, Plouzané, France 3 : Sorbonne Université, École Doctorale Complexité du Vivant (ED515), Paris, France 4 : Utech UBI, Institut Pasteur, CNRS UMR 3528, Paris, France 5 : Molecular Biophysics Platform, C2RT, Institut Pasteur, CNRS UMR 3528, Paris, France 6 : Department of Biochemistry and Biophysics, Science for Life Laboratory, Stockholm University, Stockholm, Sweden 7 : Department of Applied Physics, KTH Royal Institute of Technology, Stockholm, Sweden |
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Source | Nature Communications (2041-1723) (Nature Publishing Group), 2020-03 , Vol. 11 , N. 1 , P. 12p. | ||||||||||||||||||||||||||||||||||||
DOI | 10.1038/s41467-020-15392-9 | ||||||||||||||||||||||||||||||||||||
WOS© Times Cited | 22 | ||||||||||||||||||||||||||||||||||||
Abstract | Replicative DNA polymerases (DNAPs) have evolved the ability to copy the genome with high processivity and fidelity. In Eukarya and Archaea, the processivity of replicative DNAPs is greatly enhanced by its binding to the proliferative cell nuclear antigen (PCNA) that encircles the DNA. We determined the cryo-EM structure of the DNA-bound PolD–PCNA complex from Pyrococcus abyssi at 3.77 Å. Using an integrative structural biology approach — combining cryo-EM, X-ray crystallography, protein–protein interaction measurements, and activity assays — we describe the molecular basis for the interaction and cooperativity between a replicative DNAP and PCNA. PolD recruits PCNA via a complex mechanism, which requires two different PIP-boxes. We infer that the second PIP-box, which is shared with the eukaryotic Polα replicative DNAP, plays a dual role in binding either PCNA or primase, and could be a master switch between an initiation and a processive phase during replication. |
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