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

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.

SUBMITTER: Deshpande RA

PROVIDER: S-EPMC6949041 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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

Deshpande Rajashree A RA Myler Logan R LR Soniat Michael M MM Makharashvili Nodar N Lee Linda L Lees-Miller Susan P SP Finkelstein Ilya J IJ Paull Tanya T TT

Science advances 20200108 2

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 ...[more]

PMID: 31934630

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