title: DNA ligase I is not essential for mammalian cell viability.
abstract: Of the three DNA ligases present in all vertebrates, DNA ligase I (Lig1) has been considered essential for ligating Okazaki fragments during DNA replication and thereby essential for cell viability. Here, we report the striking finding that a Lig1-null murine B cell line is viable. Surprisingly, the Lig1-null cells exhibit normal proliferation and normal immunoglobulin heavy chain class switch recombination and are not hypersensitive to a wide variety of DNA damaging agents. These findings demonstrate that Lig1 is not absolutely required for cellular DNA replication and repair and that either Lig3 or Lig4 can substitute for the role of Lig1 in joining Okazaki fragments. The establishment of a Lig1-null cell line will greatly facilitate the characterization of DNA ligase function in mammalian cells, but the finding alone profoundly reprioritizes the role of ligase I in DNA replication, repair, and recombination.
authors.affiliation: Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI 48824, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Han
authors.affiliation: Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI 48824, USA.
authors.forename: Shahnaz
authors.initials: S
authors.lastname: Masani
authors.affiliation: Department of Urology and Department of Biochemistry and Molecular Biology, University of Southern California, Los Angeles, CA 90089, USA.
authors.forename: Chih-Lin
authors.initials: CL
authors.lastname: Hsieh
authors.affiliation: Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI 48824, USA. Electronic address: yuke@msu.edu.
authors.forename: Kefei
authors.initials: K
authors.lastname: Yu
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D004247:DNA / Q000378:metabolism; D000072481:DNA Ligase ATP; D011088:DNA Ligases / Q000235:genetics / Q000378:metabolism*; D004261:DNA Replication; D017353:Gene Deletion; D051379:Mice; D000075223:Poly-ADP-Ribose Binding Proteins; D029867:Xenopus Proteins
chemical_list: C000607894:Lig1 protein, mouse; C022262:Okazaki fragments; D000075223:Poly-ADP-Ribose Binding Proteins; D029867:Xenopus Proteins; D004247:DNA; D011088:DNA Ligases; D000072481:DNA Ligase ATP; C000618816:DNA ligase III alpha protein, Xenopus; C000618818:Lig3 protein, mouse
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