title: Redundant function of DNA ligase 1 and 3 in alternative end-joining during immunoglobulin class switch recombination.
abstract: Nonhomologous end-joining (NHEJ) is the major DNA double-strand break (DSB) repair pathway in mammals and resolves the DSBs generated during both V(D)J recombination in developing lymphocytes and class switch recombination (CSR) in antigen-stimulated B cells. In contrast to the absolute requirement for NHEJ to resolve DSBs associated with V(D)J recombination, DSBs associated with CSR can be resolved in NHEJ-deficient cells (albeit at a reduced level) by a poorly defined alternative end-joining (A-EJ) pathway. Deletion of DNA ligase IV (Lig4), a core component of the NHEJ pathway, reduces CSR efficiency in a mouse B-cell line capable of robust cytokine-stimulated CSR in cell culture. Here, we report that CSR levels are not further reduced by deletion of either of the two remaining DNA ligases (Lig1 and nuclear Lig3) in Lig4(-/-) cells. We conclude that in the absence of Lig4, Lig1, and Lig3 function in a redundant manner in resolving switch region DSBs during CSR.
authors.affiliation: Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI 48824.
authors.forename: Shahnaz
authors.initials: S
authors.lastname: Masani
authors.affiliation: Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI 48824.
authors.forename: Li
authors.initials: L
authors.lastname: Han
authors.affiliation: Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI 48824.
authors.forename: Katheryn
authors.initials: K
authors.lastname: Meek
authors.affiliation: Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI 48824 yuke@msu.edu.
authors.forename: Kefei
authors.initials: K
authors.lastname: Yu
mesh_terms: D000818:Animals; D002460:Cell Line; D002467:Cell Nucleus / Q000201:enzymology; D004249:DNA Damage; D059766:DNA End-Joining Repair; D000072481:DNA Ligase ATP; D011088:DNA Ligases / Q000235:genetics / Q000378:metabolism*; D017578:Immunoglobulin Class Switching / Q000235:genetics*; D051379:Mice; D000075223:Poly-ADP-Ribose Binding Proteins; D011995:Recombination, Genetic; D029867:Xenopus Proteins
chemical_list: C000607894:Lig1 protein, mouse; D000075223:Poly-ADP-Ribose Binding Proteins; D029867:Xenopus Proteins; D011088:DNA Ligases; D000072481:DNA Ligase ATP; C000618816:DNA ligase III alpha protein, Xenopus; C000618818:Lig3 protein, mouse
keywords: DNA double-strand break; DNA ligase; DNA repair; class switch recombination; nonhomologous end-joining