ATP‐dependent DNA binding, unwinding, and resection by the Mre11/Rad50 complex. (30th December 2015)

• Record Type: Journal Article
• Authors: Liu, Yaqi; Sung, Sihyun; Kim, Youngran; Li, Fuyang; Gwon, Gwanghyun; Jo, Aera; Kim, Ae‐Kyoung; Kim, Taeyoon; Song, Ok‐kyu; Lee, Sang Eun; Cho, Yunje
• Is Part Of: EMBO journal. Volume 35:Number 7(2016)
• Page Start: 743
• Page End: 758
• Publication Date: 2015-12-30
• Subjects: central groove -- DNA binding -- DNA melting -- Mre11/Rad50 -- nuclease; Molecular biology -- Periodicals; 572.805
• DOI: 10.15252/embj.201592462
• Languages: English
• ISSNs: 0261-4189

Abstract

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. Synopsis: The X‐ray structure of the ATP loaded Mre11/Rad50 DNA repair complex shows that DNA runs along a groove between the Rad50 dimers. ATP hydrolysis causes DNA melting and a conformational change, allowing access to Mre11 active site. Rad50 binds the DNA minor groove via a groove between the Rad50 dimer subunits. The Mre11 active site in the full‐length MR complex accesses melted but not duplex DNA. ATP hydrolysis‐driven lobe‐rotation results in partial DNA unwinding, enabling DNA to access the Mre11 active site. The structure may indicate that the MR complex recognizes DNA a few bases away from the break end. Abstract : The X‐ray structure of the ATP loaded Mre11/Rad50 DNA repair complex shows that DNA runs along a groove between the Rad50 dimers. ATP hydrolysis causes DNA melting and a conformational change, allowing access to Mre11 active site.