title: Reduced repair of DNA double-strand breaks by homologous recombination in a DNA ligase I-deficient human cell line.
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.
authors.affiliation: Radiation Oncology Research Laboratory, Department of Radiation Oncology and Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
authors.forename: Julie Della-Maria
authors.initials: JD
authors.lastname: Goetz
authors.forename: Teresa A
authors.initials: TA
authors.lastname: Motycka
authors.forename: Minguang
authors.initials: M
authors.lastname: Han
authors.forename: Maria
authors.initials: M
authors.lastname: Jasin
authors.forename: Alan E
authors.initials: AE
authors.lastname: Tomkinson
mesh_terms: D002460:Cell Line; D004249:DNA Damage; D000072481:DNA Ligase ATP; D011088:DNA Ligases / Q000172:deficiency* / Q000378:metabolism*; D004260:DNA Repair; D006801:Humans; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D011995:Recombination, Genetic
chemical_list: C000607892:LIG1 protein, human; D018809:Proliferating Cell Nuclear Antigen; D011088:DNA Ligases; D000072481:DNA Ligase ATP