Open AccessDifferent Roles for Nonhomologous End Joining and Homologous Recombination following Replication Arrest in Mammalian Cells
Author(s) -
Cecilia Lundin,
Klaus Erixon,
Catherine Arnaudeau,
Niklas Schultz,
Dag Jenssen,
Mark Meuth,
Thomas Helleday
Publication year - 2002
Publication title -
molecular and cellular biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.14
H-Index - 327
eISSN - 1067-8824
pISSN - 0270-7306
DOI - 10.1128/mcb.22.16.5869-5878.2002
Subject(s) - biology , non homologous end joining , homologous recombination , dna replication , dna repair , homologous chromosome , replication protein a , homology directed repair , microbiology and biotechnology , dna , thymidine , genetics , dna binding protein , dna mismatch repair , gene , transcription factor
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.