Han L et al. (2014), DNA ligase I is not essential for mammalian cel...

XB-ART-53411

Cell Rep 2014 Apr 24;72:316-320. doi: 10.1016/j.celrep.2014.03.024.

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DNA ligase I is not essential for mammalian cell viability.

Han L , Masani S , Hsieh CL , Yu K .

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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.

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Species referenced: Xenopus
Genes referenced: lig1 lig3 lig4

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	Figure 2. Proliferation and Drug Sensitivity of Lig1-Null CH12F3 Cells(A) Live cell counts of wild-type (WT) and Lig1-null (P/Δ) cells in cultures with (stimulated) or without (unstimulated) cytokines (see Experimental Procedures) for inducing CSR.(B) Sensitivity of wild-type (WT) and Lig1-null (Δ/Δ) cells to several DNA damaging agents. Error bars represent SEM of three independent experiments.
	Figure 3. A Metaphase of Lig1-Null CellAll the abnormal chromosomes, two copies of the normal chromosome 14, and the sex chromosome are as marked. The der(1) is the only abnormality (marked with solid arrowhead) in comparison with the parental cells, which has a chromosome count of 41.
	Figure 4. CSR of Lig1-Null CH12F3 CellsRepresentative FACS analysis of CSR by surface staining of IgA after 72 hr of growth with (stimulated) or without (unstimulated) cytokines (see the Experimental Procedures). Numbers in the boxed areas indicate percentages.