ATP‐dependent DNA binding,unwinding, and resection by the Mre11/Rad50 complex |
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| Authors: | Fuyang Li Gwanghyun Gwon Aera Jo Ae‐Kyoung Kim Taeyoon Kim Ok‐kyu Song Sang Eun Lee Yunje Cho |
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| Affiliation: | 1. Department of Molecular Medicine, Institute of Biotechnology, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA;2. Department of Radiation Oncology, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA;3. Department of Life Sciences, Pohang University of Science and Technology, Pohang, South Korea;4. Panbionet Corporation, Pohang, South Korea |
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| 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. |
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| Keywords: | central groove DNA binding DNA melting Mre11/Rad50 nuclease |
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