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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References [+] :

Alt, Mechanisms of programmed DNA lesions and genomic instability in the immune system. 2013, Pubmed

Alt, Mechanisms of programmed DNA lesions and genomic instability in the immune system. 2013, Pubmed
Arakawa, Functional redundancy between DNA ligases I and III in DNA replication in vertebrate cells. 2012, Pubmed , Xenbase
Bentley, DNA ligase I is required for fetal liver erythropoiesis but is not essential for mammalian cell viability. 1996, Pubmed
Bentley, DNA ligase I null mouse cells show normal DNA repair activity but altered DNA replication and reduced genome stability. 2002, Pubmed
Boboila, Robust chromosomal DNA repair via alternative end-joining in the absence of X-ray repair cross-complementing protein 1 (XRCC1). 2012, Pubmed
Boboila, Alternative end-joining catalyzes class switch recombination in the absence of both Ku70 and DNA ligase 4. 2010, Pubmed
Boboila, Alternative end-joining catalyzes robust IgH locus deletions and translocations in the combined absence of ligase 4 and Ku70. 2010, Pubmed
Ellenberger, Eukaryotic DNA ligases: structural and functional insights. 2008, Pubmed
Frank, DNA ligase IV deficiency in mice leads to defective neurogenesis and embryonic lethality via the p53 pathway. 2000, Pubmed
Grawunder, DNA ligase IV is essential for V(D)J recombination and DNA double-strand break repair in human precursor lymphocytes. 1998, Pubmed
Han, Altered kinetics of nonhomologous end joining and class switch recombination in ligase IV-deficient B cells. 2008, Pubmed
Han, X-ray repair cross-complementing protein 1 (XRCC1) deficiency enhances class switch recombination and is permissive for alternative end joining. 2012, Pubmed
Paul, DNA ligases I and III cooperate in alternative non-homologous end-joining in vertebrates. 2013, Pubmed , Xenbase
Petrini, DNA ligase I mediates essential functions in mammalian cells. 1995, Pubmed , Xenbase
Puebla-Osorio, Early embryonic lethality due to targeted inactivation of DNA ligase III. 2006, Pubmed , Xenbase
Simsek, Crucial role for DNA ligase III in mitochondria but not in Xrcc1-dependent repair. 2011, Pubmed , Xenbase
Yan, IgH class switching and translocations use a robust non-classical end-joining pathway. 2007, Pubmed

	Figure 2. Proliferation and Drug Sensitivity of Lig1-Null CH12F3 Cells(A) Live cell counts of wild-type (WT) and Lig1-null (P/Î) cells in cultures with (stimulated) or without (unstimulated) cytokines (see Experimental Procedures) for inducing CSR.(B) Sensitivity of wild-type (WT) and Lig1-null (Î/Î) 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.