Reduced repair of DNA double-strand breaks by homologous recombination in a DNA ligase I-deficient human cell line》.pdf

DNA Repair 4 (2005) 649–654 Reduced repair of DNA double-strand breaks by homologous recombination in a DNA ligase I-deficient human cell line Julie Della-Maria Goetz a , Teresa A. Motycka a , Minguang Hanb , Maria Jasin b , Alan E. Tomkinson a,∗ a Radiation Oncology Research Laboratory, Department of Radiation Oncology and Greenebaum Cancer Center, University of Maryland School of Medicine, 6 West Baltimore Street, Baltimore, MD 21201, USA b Molecular Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA Received 1 December 2004; accepted 10 February 2005 Available online 7 April 2005 Abstract Genetic and biochemical studies of mammalian DNA ligase I indicate that this multifunctional enzyme plays a key role in the completion of DNA replication and certain DNA excision repair pathways. However, the involvement of DNA ligase I in DNA double-strand break repair has not been examined. Here we have determined the effect of DNA ligase I-deficiency on the frequency of homologous recombination initiated by a site-specific DNA double-strand break. We found that expression of wild-type DNA ligase I in a human DNA ligase I mutant cell line significantly increased the frequency of homologous recombination. Notably, the ability of DNA ligase I to promote the recombinational repair of DNA double-strand breaks was dependent upon its interaction with proliferating cell nuclear antigen. Thus, our results demonstrate that DNA ligase I-deficiency reduces recombinational repair of DNA double-strand breaks. © 2005 Elsevier B.V. All rights reserved. Keywords: DNA ligase I; DNA double-strand break repair;