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ATP-dependent DNA binding, unwinding, and resection by the Mre11/Rad50 complex.

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-ATP?S-DNA structure reveals that the partly deformed DNA runs symmetrically across central groove between two ATP?S-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.

SUBMITTER: Liu Y

PROVIDER: S-EPMC4818763 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature

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ATP-dependent DNA binding, unwinding, and resection by the Mre11/Rad50 complex.

Liu Yaqi Y Sung Sihyun S Kim Youngran Y Li Fuyang F Gwon Gwanghyun G Jo Aera A Kim Ae-Kyoung AK Kim Taeyoon T Song Ok-Kyu OK Lee Sang Eun SE Cho Yunje Y

The EMBO journal 20151230 7

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 Mre ...[more]

PMID: 26717941

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