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Nej1 Interacts with Mre11 to Regulate-Tethering and Dna2 Binding at DNA Double-Strand Breaks

40 Pages Posted: 15 Mar 2019 Sneak Peek Status: Published

See all articles by Aditya Mojumdar

Aditya Mojumdar

University of Calgary - Department of Biochemistry and Molecular Biology; University of Calgary - Department of Oncology

Kyle Sorenson

University of Calgary - Department of Biochemistry and Molecular Biology; University of Calgary - Department of Oncology

Marcel Hohl

Memorial Sloan Kettering Cancer Center - Molecular Biology Program

Susan Lees-Miller

University of Calgary - Department of Biochemistry and Molecular Biology; University of Calgary - Department of Oncology

Karine Dubrana

University of Paris-Saclay - Laboratory Instability and Nuclear Organization

John Petrini

Memorial Sloan Kettering Cancer Center - Molecular Biology Program

Jennifer A. Cobb

University of Calgary - Department of Biochemistry and Molecular Biology; University of Calgary - Department of Oncology

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Abstract

Non-homologous end-joining (NHEJ) and homologous recombination (HR) are the two major pathways of DNA double strand break (DSB) repair and both are highly conserved from yeast to mammals. Nej1 has a role in DNA end tethering and the Mre11/Rad50/Xrs2 (MRX) complex is important for its recruitment to a DSB. Nej1 and Dna2- Sgs1 interact with the C-terminal end of Mre11, which also includes the region where Rad50 binds. Characterization of Nej1 in two rad50 mutants that alter the structural features of MRX showed that Nej1 inhibits Dna2 interactions with Mre11 and Sgs1. The work support a model whereby Nej1 binding to Mre11 provides a layer of regulation to repair pathway choice at the DSB.

Keywords: DSB repair, NHEJ, Nej1, Mre11-Rad50-Xrs2 (MRX), 5’ resection, end-tethering

Suggested Citation

Mojumdar, Aditya and Sorenson, Kyle and Hohl, Marcel and Lees-Miller, Susan and Dubrana, Karine and Petrini, John and Cobb, Jennifer A., Nej1 Interacts with Mre11 to Regulate-Tethering and Dna2 Binding at DNA Double-Strand Breaks (March 14, 2019). Available at SSRN: https://ssrn.com/abstract=3352501 or http://dx.doi.org/10.2139/ssrn.3352501
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Aditya Mojumdar

University of Calgary - Department of Biochemistry and Molecular Biology

University Drive
Calgary, Alberta T2N 1N4
Canada

University of Calgary - Department of Oncology

University Drive
Calgary, Alberta T2N 1N4
Canada

Kyle Sorenson

University of Calgary - Department of Biochemistry and Molecular Biology

University Drive
Calgary, Alberta T2N 1N4
Canada

University of Calgary - Department of Oncology

University Drive
Calgary, Alberta T2N 1N4
Canada

Marcel Hohl

Memorial Sloan Kettering Cancer Center - Molecular Biology Program

New York, NY 10065
United States

Susan Lees-Miller

University of Calgary - Department of Biochemistry and Molecular Biology

University Drive
Calgary, Alberta T2N 1N4
Canada

University of Calgary - Department of Oncology

University Drive
Calgary, Alberta T2N 1N4
Canada

Karine Dubrana

University of Paris-Saclay - Laboratory Instability and Nuclear Organization

55 Avenue de Paris
Versailles, 78000
France

John Petrini

Memorial Sloan Kettering Cancer Center - Molecular Biology Program

New York, NY 10065
United States

Jennifer A. Cobb (Contact Author)

University of Calgary - Department of Biochemistry and Molecular Biology ( email )

University Drive
Calgary, Alberta T2N 1N4
Canada

University of Calgary - Department of Oncology ( email )

University Drive
Calgary, Alberta T2N 1N4
Canada

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