QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

Vol. 17, Issue 10, 4473-4483, October 2006

This Article Full Text Full Text (PDF) Supplemental Material All Versions of this Article: E06-06-0516v1 17/10/4473    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Mankouri, H. W. Articles by Hickson, I. D. Search for Related Content PubMed PubMed Citation Articles by Mankouri, H. W. Articles by Hickson, I. D.

Top3 Processes Recombination Intermediates and Modulates Checkpoint Activity after DNA Damage

Cancer Research UK Laboratories, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DS, United Kingdom

Submitted June 12, 2006; Revised July 28, 2006; Accepted July 31, 2006
Monitoring Editor: Wendy Bickmore

Mutation of TOP3 in Saccharomyces cerevisiae causes poor growth, hyperrecombination, and a failure to fully activate DNA damage checkpoints in S phase. Here, we report that overexpression of a dominant-negative allele of TOP3, TOP3^Y356F, which lacks the catalytic (decatenation) activity of Top3, causes impaired S-phase progression and the persistence of abnormal DNA structures (X-shaped DNA molecules) after exposure to methylmethanesulfonate. The impaired S-phase progression is due to a persistent checkpoint-mediated cell cycle delay and can be overridden by addition of caffeine. Hence, the catalytic activity of Top3 is not required for DNA damage checkpoint activation, but it is required for normal S-phase progression after DNA damage. We also present evidence that the checkpoint-mediated cell cycle delay and persistence of X-shaped DNA molecules resulting from overexpression of TOP3^Y356F are downstream of Rad51 function. We propose that Top3 functions in S phase to both process homologous recombination intermediates and modulate checkpoint activity.

This article was published online ahead of print in MBC in Press (http://www.molbiolcell.org/cgi/doi/10.1091/mbc.E06-06-0516) on August 9, 2006.

Address correspondence to: Ian D. Hickson (ian.hickson{at}cancer.org.uk)

Abbreviations used: HR, homologous recombination.

This article has been cited by other articles:

				H. W. Mankouri, H.-P. Ngo, and I. D. Hickson Esc2 and Sgs1 Act in Functionally Distinct Branches of the Homologous Recombination Repair Pathway in Saccharomyces cerevisiae Mol. Biol. Cell, March 15, 2009; 20(6): 1683 - 1694. [Abstract] [Full Text] [PDF]

				S. Mohanty, T. Town, T. Yagi, C. Scheidig, K. Y. Kwan, H. G. Allore, R. A. Flavell, and A. C. Shaw Defective p53 engagement after the induction of DNA damage in cells deficient in topoisomerase 3{beta} PNAS, April 1, 2008; 105(13): 5063 - 5068. [Abstract] [Full Text] [PDF]

				H. W. Mankouri, H.-P. Ngo, and I. D. Hickson Shu Proteins Promote the Formation of Homologous Recombination Intermediates That Are Processed by Sgs1-Rmi1-Top3 Mol. Biol. Cell, October 1, 2007; 18(10): 4062 - 4073. [Abstract] [Full Text] [PDF]