Ctf4 is a hub in the eukaryotic replisome that links multiple CIP-box proteins to the CMG helicase

Fabrizio Villa, Aline C. Simon, Maria Angeles Ortiz Bazan, Mairi L. Kilkenny, David Wirthensohn, Mel Wightman, Dijana Matak-Vinkovíc, Luca Pellegrini (Lead / Corresponding author), Karim Labib (Lead / Corresponding author)

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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 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.
Original languageEnglish
Pages (from-to)385-396
Number of pages12
JournalMolecular Cell
Volume63
Issue number3
Early online date7 Jul 2016
DOIs
Publication statusPublished - 4 Aug 2016

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    Villa, F., Simon, A. C., Ortiz Bazan, M. A., Kilkenny, M. L., Wirthensohn, D., Wightman, M., Matak-Vinkovíc, D., Pellegrini, L., & Labib, K. (2016). Ctf4 is a hub in the eukaryotic replisome that links multiple CIP-box proteins to the CMG helicase. Molecular Cell, 63(3), 385-396. https://doi.org/10.1016/j.molcel.2016.06.009