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Molecular and Cellular Biology, August 2002, p. 5869-5878, Vol. 22, No. 16
0270-7306/02/$04.00+0     DOI: 10.1128/MCB.22.16.5869-5878.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Different Roles for Nonhomologous End Joining and Homologous Recombination following Replication Arrest in Mammalian Cells

Cecilia Lundin,1 Klaus Erixon,1 Catherine Arnaudeau,1,{dagger} Niklas Schultz,1 Dag Jenssen,1 Mark Meuth,2 and Thomas Helleday1,2*

Department of Genetic and Cellular Toxicology, Stockholm University, S-106 91 Stockholm, Sweden,1 The Institute for Cancer Studies, University of Sheffield, Sheffield S10 2RX, United Kingdom2

Received 20 March 2002/ Returned for modification 18 April 2002/ Accepted 20 May 2002

Homologous recombination (HR) and nonhomologous end joining (NHEJ) play overlapping roles in repair of DNA double-strand breaks (DSBs) generated during the S phase of the cell cycle. Here, we characterized the involvement of HR and NHEJ in the rescue of DNA replication forks arrested or slowed by treatment of hamster cells with hydroxyurea or thymidine. We show that the arrest of replication with hydroxyurea generates DNA fragmentation as a consequence of the formation of DSBs at newly replicated DNA. Both HR and NHEJ protected cells from the lethal effects of hydroxyurea, and this agent also increased the frequency of recombination mediated by both homologous and nonhomologous exchanges. Thymidine induced a less stringent arrest of replication and did not generate detectable DSBs. HR alone rescued cells from the lethal effects of thymidine. Furthermore, thymidine increased the frequency of DNA exchange mediated solely by HR in the absence of detectable DSBs. Our data suggest that both NHEJ and HR are involved in repair of arrested replication forks that include a DSB, while HR alone is required for the repair of slowed replication forks in the absence of detectable DSBs.

* Corresponding author. Mailing address: The Institute for Cancer Studies, University of Sheffield, Beech Hill Road, Sheffield S10 2RX, United Kingdom. Phone: 44-114 271 2993. Fax: 44-114 271 3515. E-mail: t.helleday{at}sheffield.ac.uk.

{dagger} Present address: Institute for Cancer Research, 94801 Villejuif, France.

Molecular and Cellular Biology, August 2002, p. 5869-5878, Vol. 22, No. 16
0022-538X/02/$04.00+0     DOI: 10.1128/MCB.22.16.5869-5878.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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