DNA-PKcs phosphorylation at the T2609 cluster alters the repair pathway choice during immunoglobulin class switch recombination | Zendy

Jennifer Crowe | Zendy; Xiaobin S. Wang | Zendy; Zhengping Shao | Zendy; Brian J. Lee | Zendy; Verna M. Estes | Zendy; Shan Zha | Zendy

Open Access

DNA-PKcs phosphorylation at the T2609 cluster alters the repair pathway choice during immunoglobulin class switch recombination

Author(s) -

Jennifer Crowe,

Xiaobin S. Wang,

Zhengping Shao,

Brian J. Lee,

Verna M. Estes,

Shan Zha

Publication year - 2020

Publication title -

proceedings of the national academy of sciences

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 5.011

H-Index - 771

eISSN - 1091-6490

pISSN - 0027-8424

DOI - 10.1073/pnas.2007455117

Subject(s) - dna pkcs , phosphorylation , v(d)j recombination , dna repair , dna , non homologous end joining , immunoglobulin class switching , dna repair protein xrcc4 , microbiology and biotechnology , recombination , protein subunit , biology , protein kinase a , chemistry , genetics , antibody , gene , dna mismatch repair , b cell

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.

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