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 Eun Lee; Yunje Cho

doi:10.15252/embj.201592462

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 Eun Lee, Yunje Cho

Research output: Contribution to journal › Article › peer-review

83 Scopus citations

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 language	English (US)
Pages (from-to)	743-758
Number of pages	16
Journal	EMBO Journal
Volume	35
Issue number	7
DOIs	https://doi.org/10.15252/embj.201592462
State	Published - Apr 1 2016
Externally published	Yes

Keywords

DNA binding
DNA melting
Mre11/Rad50
central groove
nuclease

ASJC Scopus subject areas

General Neuroscience
Molecular Biology
General Biochemistry, Genetics and Molecular Biology
General Immunology and Microbiology

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10.15252/embj.201592462

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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.",

keywords = "DNA binding, DNA melting, Mre11/Rad50, central groove, nuclease",

author = "Yaqi Liu and Sihyun Sung and Youngran Kim and Fuyang Li and Gwanghyun Gwon and Aera Jo and Kim, {Ae Kyoung} and Taeyoon Kim and Song, {Ok Kyu} and Lee, {Sang Eun} and Yunje Cho",

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doi = "10.15252/embj.201592462",

language = "English (US)",

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T1 - ATP-dependent DNA binding, unwinding, and resection by the Mre11/Rad50 complex

AU - Liu, Yaqi

AU - Sung, Sihyun

AU - Kim, Youngran

AU - Li, Fuyang

AU - Gwon, Gwanghyun

AU - Jo, Aera

AU - Kim, Ae Kyoung

AU - Kim, Taeyoon

AU - Song, Ok Kyu

AU - Lee, Sang Eun

AU - Cho, Yunje

PY - 2016/4/1

Y1 - 2016/4/1

N2 - 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.

AB - 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.

KW - DNA binding

KW - DNA melting

KW - Mre11/Rad50

KW - central groove

KW - nuclease

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SN - 0261-4189

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JO - EMBO Journal

JF - EMBO Journal

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

Abstract

Keywords

ASJC Scopus subject areas

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