Abstract
ATP-dependent DNA end recognition and nucleolytic processing are central functions of the Mre11/Rad50 (MR) complex in DNA double-strand break repair. However, it is still unclear how ATP binding and hydrolysis primes the MR function and regulates repair pathway choice in cells. Here, Methanococcus jannaschii MR-ATPγS-DNA structure reveals that the partly deformed DNA runs symmetrically across central groove between two ATPγS-bound Rad50 nucleotide-binding domains. Duplex DNA cannot access the Mre11 active site in the ATP-free full-length MR complex. ATP hydrolysis drives rotation of the nucleotide-binding domain and induces the DNA melting so that the substrate DNA can access Mre11. Our findings suggest that the ATP hydrolysis-driven conformational changes in both DNA and the MR complex coordinate the melting and endonuclease activity.
Original language | English (US) |
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Pages (from-to) | 743-758 |
Number of pages | 16 |
Journal | EMBO Journal |
Volume | 35 |
Issue number | 7 |
DOIs | |
State | Published - Apr 1 2016 |
Externally published | Yes |
Keywords
- DNA binding
- DNA melting
- Mre11/Rad50
- central groove
- nuclease
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
- Immunology and Microbiology(all)
- Molecular Biology
- Neuroscience(all)