Nucleic Acids Research Advance Access originally published online on August 8, 2007
Nucleic Acids Research 2007 35(16):5323-5337; doi:10.1093/nar/gkm527
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Nucleic Acids Research, 2007, Vol. 35, No. 16 5323-5337
© 2007 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Molecular Biology |
Cdc18/CDC6 activates the Rad3-dependent checkpoint in the fission yeast
Cell Cycle Group, Cancer Research UK London Institute, London WC2A 3PX, UK.
*To whom correspondence should be addressed. Tel: +44 845155 5000; Fax: +44 207 3809314; Email: naomi.fersht{at}yahoo.co.uk
Received January 27, 2007. Revised June 24, 2007. Accepted June 25, 2007.
A screen for genes that can ectopically activate a Rad3-dependent checkpoint block over mitosis in fission yeast has identified the DNA replication initiation factor cdc18 (known as CDC6 in other organisms). Either a stabilized form of Cdc18, the Cdc18-T6A phosphorylation mutant, or overexpression of wild type Cdc18, activate the Rad3-dependent S-M checkpoint in the apparent absence of detectable replication structures and gross DNA damage. This cell cycle block relies on the Rad checkpoint pathway and requires Chk1 phosphorylation and activation. Unexpectedly, Cdc18-T6A induces changes in the mobility of Chromosome III, affecting the size of a restriction fragment containing rDNA repeats and producing aberrant nucleolar structures. Recombination events within the rDNA appear to contribute at least in part to the cell cycle delay. We propose that an elevated level of Cdc18 activates the Rad3-dependent checkpoint either directly or indirectly, and additionally causes expansion of the rDNA repeats on Chromosome III.
Present address: Naomi Fersht, Department of Oncology, University College Hospital London, London NW1 2BU, UK Damien Hermand, FUNDP-GEMO, 5000 Namur, Belgium Paul Nurse, The Rockefeller University, New York 10021, USA
The authors wish it to be known that, in their opinion, the first two authors should be regarded as joint First Authors.
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