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Ctf4 Is a Hub in the Eukaryotic Replisome that Links Multiple CIP-Box Proteins to the CMG Helicase

DOI: 10.1016/j.molcel.2016.06.009 DOI Help

Authors: Fabrizio Villa (MRC Protein Phosphorylation and Ubiquitylation Unit, University of Dundee) , Aline Simon (University of Cambridge) , Maria angeles Ortiz bazan (MRC Protein Phosphorylation and Ubiquitylation Unit, University of Dundee) , Mairi Kilkenny (Department of Biochemistry, University of Cambridge) , David Wirthensohn (Department of Chemistry, University of Cambridge) , Mel Wightman (MRC Protein Phosphorylation and Ubiquitylation Unit, University of Dundee) , Dijana Matak-vinkovíc (Department of Chemistry, University of Cambridge) , Luca Pellegrini (University of Cambridge, U.K.) , Karim Labib (MRC Protein Phosphorylation and Ubiquitylation Unit, University of Dundee)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Molecular Cell , VOL 63 , PAGES 385 - 396

State: Published (Approved)
Published: August 2016

Open Access Open Access

Abstract: Replisome assembly at eukaryotic replication forks connects the DNA helicase to DNA polymerases and many other factors. The helicase binds the leading-strand polymerase directly, but is connected to the Pol alpha lagging-strand polymerase by the trimeric adaptor Ctf4. Here, we identify new Ctf4 partners inaddition to Pol alpha and helicase, all of which contain a "Ctf4-interacting-peptide" or CIP-box. Crystallographic analysis classifies CIP-boxes into two related groups that target different sites on Ctf4. Mutations in the CIP-box motifs of the Dna2 nuclease or the rDNA-associated protein Tof2 do not perturb DNA synthesis genome-wide, but instead lead to a dramatic shortening of chromosome 12 that contains the large array of rDNA repeats. Our data reveal unexpected complexity of Ctf4 function, as a hub that connects multiple accessory factors to the replisome. Most strikingly, Ctf4-dependent recruitment of CIP-box proteins couples other processes to DNA synthesis, including rDNA copy-number regulation.

Subject Areas: Biology and Bio-materials, Chemistry, Medicine


Instruments: I02-Macromolecular Crystallography

Added On: 15/08/2016 14:14

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