DNA-PKcs phosphorylation at the T2609 cluster alters the repair pathway choice during immunoglobulin class switch recombination
DNA-PKcs phosphorylation at the T2609 cluster alters the repair pathway choice during immunoglobulin class switch recombination
Significance DNA-dependent protein kinase (DNA-PK), which is composed of the KU heterodimer and the large catalytic subunit (DNA-PKcs), is a classical nonhomologous end-joining (cNHEJ) factor with important roles in immunoglobulin class switch recombination. Activated DNA-PK phosphorylates many substrates, including DNA-PKcs itself at the T2609 cluster. Using knockin mouse models, we found that while the loss of T2609 phosphorylation of DNA-PKcs does not affect class switch recombination (CSR) efficiency, the CSR junctions recovered from T2609A B cells are generated by the alternative end-joining pathway, providing the evidence for a role of DNA-PKcs T2609 phosphorylation in DNA repair pathway choice.
- King’s University United States
- Columbia University United States
- Columbia University United States
- COLUMBIA UNIVERSITY HEALTH SCIENCES
- Columbia University United States
Gene Rearrangement, Male, Recombination, Genetic, B-Lymphocytes, Mice, 129 Strain, DNA Repair, Immunoglobulins, DNA-Activated Protein Kinase, Immunoglobulin Class Switching, Translocation, Genetic, Immunoglobulin Switch Region, DNA-Binding Proteins, Mice, Animals, Humans, Female, Phosphorylation, Ku Autoantigen
Gene Rearrangement, Male, Recombination, Genetic, B-Lymphocytes, Mice, 129 Strain, DNA Repair, Immunoglobulins, DNA-Activated Protein Kinase, Immunoglobulin Class Switching, Translocation, Genetic, Immunoglobulin Switch Region, DNA-Binding Proteins, Mice, Animals, Humans, Female, Phosphorylation, Ku Autoantigen
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