Kinase-dependent structural role of DNA-PKcs during immunoglobulin class switch recombination.

ABSTRACT: The catalytic subunit of DNA-dependent protein kinase (DNA-PKcs) is a classical nonhomologous end-joining (cNHEJ) factor. Loss of DNA-PKcs diminished mature B cell class switch recombination (CSR) to other isotypes, but not IgG1. Here, we show that expression of the kinase-dead DNA-PKcs (DNA-PKcs^KD/KD ) severely compromises CSR to IgG1. High-throughput sequencing analyses of CSR junctions reveal frequent accumulation of nonproductive interchromosomal translocations, inversions, and extensive end resection in DNA-PKcs^KD/KD , but not DNA-PKcs^-/- , B cells. Meanwhile, the residual joints from DNA-PKcs^KD/KD cells and the efficient Sµ-Sγ1 junctions from DNA-PKcs^-/-

SUBMITTER: Crowe JL 

PROVIDER: S-EPMC6112704 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature