title: 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-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.
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology, Pohang, South Korea.
authors.forename: Yaqi
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology, Pohang, South Korea.
authors.forename: Sihyun
authors.initials: S
authors.lastname: Sung
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology, Pohang, South Korea.
authors.forename: Youngran
authors.initials: Y
authors.lastname: Kim
authors.affiliation: Department of Molecular Medicine, Institute of Biotechnology, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA Department of Radiation Oncology, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
authors.forename: Fuyang
authors.initials: F
authors.lastname: Li
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology, Pohang, South Korea.
authors.forename: Gwanghyun
authors.initials: G
authors.lastname: Gwon
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology, Pohang, South Korea.
authors.forename: Aera
authors.initials: A
authors.lastname: Jo
authors.affiliation: Panbionet Corporation, Pohang, South Korea.
authors.forename: Ae-Kyoung
authors.initials: AK
authors.lastname: Kim
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology, Pohang, South Korea.
authors.forename: Taeyoon
authors.initials: T
authors.lastname: Kim
authors.affiliation: Panbionet Corporation, Pohang, South Korea.
authors.forename: Ok-Kyu
authors.initials: OK
authors.lastname: Song
authors.affiliation: Department of Molecular Medicine, Institute of Biotechnology, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA Department of Radiation Oncology, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
authors.forename: Sang Eun
authors.initials: SE
authors.lastname: Lee
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology, Pohang, South Korea yunje@postech.ac.kr.
authors.forename: Yunje
authors.initials: Y
authors.lastname: Cho
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000595:Amino Acid Sequence; D019843:Archaeal Proteins / Q000737:chemistry / Q000378:metabolism*; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D017017:Methanococcus / Q000378:metabolism*; D008969:Molecular Sequence Data; D017386:Sequence Homology, Amino Acid
chemical_list: D019843:Archaeal Proteins; D000255:Adenosine Triphosphate; D004247:DNA
keywords: DNA binding; DNA melting; Mre11/Rad50; central groove; nuclease