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

Authors: Jennifer L. Crowe; Xiaobin S. Wang; Zhengping Shao; Brian J. Lee; Verna M. Estes; Shan Zha;

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

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.

Keywords

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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    citations
    This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    25
    popularity
    This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
    Top 10%
    influence
    This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    Average
    impulse
    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
    Top 10%
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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
25
Top 10%
Average
Top 10%
Green
bronze