IN-DEPTH MAPPING OF DNA-PKcs SIGNALING UNCOVERS CONSERVED FEATURES OF ITS KINASE SPECIFICITY.

ABSTRACT: DNA-PKcs is a DNA damage sensor kinase with established roles in DNA double-strand break repair via non-homologous end joining. Recent studies have revealed additional roles of DNA-PKcs in the regulation of transcription, translation and DNA replication. However, the substrates through which DNA-PKcs regulates these processes remain largely undefined. Here we utilized quantitative phosphoproteomics to generate a high coverage map of DNA-PKcs signaling in response to ionizing radiation and mapped its interplay with the ATM kinase. Beyond the detection of the canonical S/T-Q phosphorylation motif, we uncovered a non-canonical mode of DNA-PKcs signaling targeting S/T-ψ-D/E motifs. Cross-species analysis in mouse pre-B and human HCT116 cell lines revealed splicing factors and transcriptional r

SUBMITTER: Marshall S 

PROVIDER: S-EPMC10827184 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature