Format

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

1
Department of Molecular Biosciences, University of Texas at Austin, Austin, TX 78712, USA.
2
Laboratory for Cell Biology and Genetics, Rockefeller University, New York, NY 10065, USA.
3
Department of Biochemistry and Molecular Biology, University of Calgary, Alberta T2N 1N4, Canada.
4
Center for Systems and Synthetic Biology, University of Texas at Austin, Austin, TX 78712, USA.

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.

Supplemental Content

Full text links

Icon for PubMed Central
Loading ...
Support Center