DNA-dependent protein kinase promotes DNA end processing by MRN and CtIP.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 31934630.
- Also identified by DOI 10.1126/sciadv.aay0922 and PMC identifier 6949041.
- Licence recorded as CC BY-NC.
- Because redistribution is not established, this page shows the abstract only. Follow the links below for the full text.
Abstract
The repair of DNA double-strand breaks occurs through nonhomologous end joining or homologous recombination in vertebrate cells-a choice that is thought to be decided by a competition between DNA-dependent protein kinase (DNA-PK) and the Mre11/Rad50/Nbs1 (MRN) complex but is not well understood. Using ensemble biochemistry and single-molecule approaches, here, we show that the MRN complex is dependent on DNA-PK and phosphorylated CtIP to perform efficient processing and resection of DNA ends in physiological conditions, thus eliminating the competition model. Endonucleolytic removal of DNA-PK-bound DNA ends is also observed at double-strand break sites in human cells. The involvement of DNA-PK in MRN-mediated end processing promotes an efficient and sequential transition from nonhomologous end joining to homologous recombination by facilitating DNA-PK removal.
Medical subject headings
- DNA
- DNA-Activated Protein Kinase
- Endodeoxyribonucleases
- Multiprotein Complexes