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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
Authors:
Fabrizio
Villa
(University of Dundee)
,
Aline
Simon
(University of Cambridge)
,
Maria angeles
Ortiz bazan
(University of Dundee)
,
Mairi
Kilkenny
(University of Cambridge)
,
David
Wirthensohn
(University of Cambridge)
,
Mel
Wightman
(University of Dundee)
,
Dijana
Matak-Vinkovíc
(University of Cambridge)
,
Luca
Pellegrini
(University of Cambridge, U.K.)
,
Karim
Labib
(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

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
Instruments:
I02-Macromolecular Crystallography
Added On:
15/08/2016 14:14
Discipline Tags:
Biochemistry
Chemistry
Structural biology
Life Sciences & Biotech
Technical Tags:
Diffraction
Macromolecular Crystallography (MX)