Structural insights into inhibitor regulation of the DNA repair protein DNA-PKcs.

ABSTRACT: The DNA-dependent protein kinase catalytic subunit (DNA-PKcs) has a central role in non-homologous end joining, one of the two main pathways that detect and repair DNA double-strand breaks (DSBs) in humans^1,2. DNA-PKcs is of great importance in repairing pathological DSBs, making DNA-PKcs inhibitors attractive therapeutic agents for cancer in combination with DSB-inducing radiotherapy and chemotherapy³. Many of the selective inhibitors of DNA-PKcs that have been developed exhibit potential as treatment for various cancers⁴. Here we report cryo-electron microscopy (cryo-EM) structures of human DNA-PKcs natively purified from HeLa cell nuclear extracts, in complex with adenosine-5'-(γ-thio)-triphosphate (ATPγS) and four inhibitors (wortmannin, NU7441, AZD7648

SUBMITTER: Liang S 

PROVIDER: S-EPMC8791830 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature