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Article
Subject Categories: Cell Cycle | Genomic & Computational Biology
The EMBO Journal (2007) 26, 1315–1326, doi:10.1038/sj.emboj.7601538
Published online 15 February 2007
Replication foci dynamics: replication patterns are modulated by S-phase checkpoint kinases in fission yeast
Peter Meister1, 2, Angela Taddei1, 3, Aaron Ponti1, Giuseppe Baldacci2, 4 and Susan M Gasser1, 4
1 Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland
2 UMR2027, CNRS/Institut Curie, Bâtiment 110, Centre Universitaire, Orsay Cedex, France
3 UMR218, CNRS/Institut Curie, 26 rue d'Ulm, Paris, France
4 These authors contributed equally to this work

To whom correspondence should be addressed
Susan M Gasser, Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland. Tel.: +41 61 697 7255; Fax +41 61 697 6862; E-mail: susan.gasser@fmi.ch

Received 21 August 2006; Accepted 11 December 2006; Published online 15 February 2007.
Abstract
Although the molecular enzymology of DNA replication is well characterised, how and why it occurs in discrete nuclear foci is unclear. Using fission yeast, we show that replication takes place in a limited number of replication foci, whose distribution changes with progression through S phase. These sites define replication factories which contain on average 14 replication forks. We show for the first time that entire foci are mobile, able both to fuse and re-segregate. These foci form distinguishable patterns during S phase, whose succession is reproducible, defining early-, mid- and late-S phase. In wild-type cells, this same temporal sequence can be detected in the presence of hydroxyurea (HU), despite the reduced rate of replication. In cells lacking the intra-S checkpoint kinase Cds1, replication factories dismantle on HU. Intriguingly, even in the absence of DNA damage, the replication foci in cds1 cells assume a novel distribution that is not present in wild-type cells, arguing that Cds1 kinase activity contributes to the spatio-temporal organisation of replication during normal cell growth.
Keywords: nuclear organisation, replication foci, replication timing, S-phase checkpoint
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