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

Yaqi Liu, Sihyun Sung, Youngran Kim, Fuyang Li, Gwanghyun Gwon, Aera Jo, Ae Kyoung Kim, Taeyoon Kim, Ok kyu Song, Sang Lee, Yunje Cho

Research output: Contribution to journalArticle

28 Citations (Scopus)

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 languageEnglish (US)
JournalEMBO Journal
DOIs
StateAccepted/In press - 2015

Fingerprint

Adenosine Triphosphate
DNA
Hydrolysis
Nucleotides
Methanocaldococcus
Nucleic Acid Denaturation
Melting
Repair
Double-Stranded DNA Breaks
Endonucleases
Freezing
Catalytic Domain
Substrates
Processing

Keywords

  • Central groove
  • DNA binding
  • DNA melting
  • Mre11/Rad50
  • Nuclease

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Neuroscience(all)

Cite this

Liu, Y., Sung, S., Kim, Y., Li, F., Gwon, G., Jo, A., ... Cho, Y. (Accepted/In press). ATP-dependent DNA binding, unwinding, and resection by the Mre11/Rad50 complex. EMBO Journal. https://doi.org/10.15252/embj.201592462

ATP-dependent DNA binding, unwinding, and resection by the Mre11/Rad50 complex. / Liu, Yaqi; Sung, Sihyun; Kim, Youngran; Li, Fuyang; Gwon, Gwanghyun; Jo, Aera; Kim, Ae Kyoung; Kim, Taeyoon; Song, Ok kyu; Lee, Sang; Cho, Yunje.

In: EMBO Journal, 2015.

Research output: Contribution to journalArticle

Liu, Y, Sung, S, Kim, Y, Li, F, Gwon, G, Jo, A, Kim, AK, Kim, T, Song, OK, Lee, S & Cho, Y 2015, 'ATP-dependent DNA binding, unwinding, and resection by the Mre11/Rad50 complex', EMBO Journal. https://doi.org/10.15252/embj.201592462
Liu, Yaqi ; Sung, Sihyun ; Kim, Youngran ; Li, Fuyang ; Gwon, Gwanghyun ; Jo, Aera ; Kim, Ae Kyoung ; Kim, Taeyoon ; Song, Ok kyu ; Lee, Sang ; Cho, Yunje. / ATP-dependent DNA binding, unwinding, and resection by the Mre11/Rad50 complex. In: EMBO Journal. 2015.
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AU - Gwon, Gwanghyun

AU - Jo, Aera

AU - Kim, Ae Kyoung

AU - Kim, Taeyoon

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AU - Lee, Sang

AU - Cho, Yunje

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