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

73 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

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

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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",

note = "Funding Information: This work was supported by grants from the National Research Foundation of Korea (NRF) funded by the Korea Government (MEST, No. 2015R1A2A1A05001694, No. 2012-054226, and No. 2013M3A6A4044580), a rising Star Program (POSTECH) and BK21 Program (Ministry of Education) to Y.C. and from NIH (GM071011) to S.E.L. Coordinates and structure factors have been deposited to RCSB (5DNY and 5F3W). Publisher Copyright: {\textcopyright} 2015 The Authors.",

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doi = "10.15252/embj.201592462",

language = "English (US)",

volume = "35",

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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

N1 - Funding Information: This work was supported by grants from the National Research Foundation of Korea (NRF) funded by the Korea Government (MEST, No. 2015R1A2A1A05001694, No. 2012-054226, and No. 2013M3A6A4044580), a rising Star Program (POSTECH) and BK21 Program (Ministry of Education) to Y.C. and from NIH (GM071011) to S.E.L. Coordinates and structure factors have been deposited to RCSB (5DNY and 5F3W). Publisher Copyright: © 2015 The Authors.

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

Abstract

Keywords

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