Redundant function of DNA ligase 1 and 3 in alternative end-joining during immunoglobulin class switch recombination
| Autor: | Kefei Yu, Shahnaz Masani, Li Han, Katheryn Meek |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
DNA End-Joining Repair DNA Ligases chemical and pharmacologic phenomena LIG3 Xenopus Proteins Biology LIG4 LIG1 Immunoglobulin Class Switch Recombination Cell Line DNA Ligase ATP Mice 03 medical and health sciences chemistry.chemical_compound Animals Poly-ADP-Ribose Binding Proteins Cell Nucleus Recombination Genetic chemistry.chemical_classification DNA ligase Multidisciplinary fungi Biological Sciences Immunoglobulin Class Switching Molecular biology enzymes and coenzymes (carbohydrates) 030104 developmental biology chemistry Immunoglobulin class switching DNA DNA Damage |
| Zdroj: | Proceedings of the National Academy of Sciences. 113:1261-1266 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.1521630113 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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