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

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 α lagging-strand polymerase by the trimeric adaptor Ctf4. Here, we identify new Ctf4 partners in addition to Pol α 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.
Mesh Terms:
Binding Sites, Chromosomes, Fungal, DNA Helicases, DNA Polymerase I, DNA, Fungal, DNA, Ribosomal, DNA-Binding Proteins, Gene Dosage, Intracellular Signaling Peptides and Proteins, Models, Molecular, Multiprotein Complexes, Mutation, Protein Binding, Protein Interaction Domains and Motifs, S Phase, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Structure-Activity Relationship
Mol. Cell
Date: Aug. 04, 2016
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