DNA-PKcs phosphorylation at the T2609 cluster alters the repair pathway choice during immunoglobulin class switch recombination
Jennifer Crowe, Xiaobin S. Wang, Zhengping Shao, Brian J. Lee, Verna M. Estes, Shan Zha
Abstract
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.