DNA Ligase I Is Not Essential for Mammalian Cell Viability

Abstract

Summary: 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. : The three mammalian DNA ligases (I, III, and IV) are thought to have distinct and restricted functions in DNA replication and various forms of DNA repair. Han et al. now show that a mouse B cell line can survive without DNA ligase I, an enzyme widely regarded as essential for joining Okazaki fragments at the replication fork. These data reveal possible functional redundancy of mammalian DNA ligases in DNA replication.