Send to

Choose Destination
Sci Adv. 2020 Jan 8;6(2):eaay0922. doi: 10.1126/sciadv.aay0922. eCollection 2020 Jan.

DNA-dependent protein kinase promotes DNA end processing by MRN and CtIP.

Author information

Department of Molecular Biosciences, University of Texas at Austin, Austin, TX 78712, USA.
Laboratory for Cell Biology and Genetics, Rockefeller University, New York, NY 10065, USA.
Department of Biochemistry and Molecular Biology, University of Calgary, Alberta T2N 1N4, Canada.
Center for Systems and Synthetic Biology, University of Texas at Austin, Austin, TX 78712, USA.


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.

Supplemental Content

Full text links

Icon for PubMed Central
Loading ...
Support Center