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Xrs2 Dependent and Independent Functions of the Mre11-Rad50 Complex.
Mol Cell. 2016 10 20; 64(2):405-415.MC

Abstract

The Mre11-Rad50-Xrs2/Nbs1 (MRX/N) complex orchestrates the cellular response to DSBs through its structural, enzymatic, and signaling roles. Xrs2/Nbs1 is essential for nuclear translocation of Mre11, but its role as a component of the complex is not well defined. Here, we demonstrate that nuclear localization of Mre11 (Mre11-NLS) is able to bypass several functions of Xrs2, including DNA end resection, meiosis, hairpin resolution, and cellular resistance to clastogens. Using purified components, we show that the MR complex has equivalent activity to MRX in cleavage of protein-blocked DNA ends. Although Xrs2 physically interacts with Sae2, we found that end resection in its absence remains Sae2 dependent in vivo and in vitro. MRE11-NLS was unable to rescue the xrs2Δ defects in Tel1/ATM kinase signaling and non-homologous end joining, consistent with the role of Xrs2 as a chaperone and adaptor protein coordinating interactions between the MR complex and other repair proteins.

Authors+Show Affiliations

Department of Biological Sciences, Columbia University, New York, NY 10027, USA; Department of Microbiology & Immunology, Columbia University Medical Center, New York, NY 10032, USA.Department of Biological Sciences, Columbia University, New York, NY 10027, USA; Department of Microbiology & Immunology, Columbia University Medical Center, New York, NY 10032, USA.Institute of Molecular Cancer Research, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland.Institute of Molecular Cancer Research, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland.Department of Microbiology & Immunology, Columbia University Medical Center, New York, NY 10032, USA. Electronic address: lss5@cumc.columbia.edu.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

27746018

Citation

Oh, Julyun, et al. "Xrs2 Dependent and Independent Functions of the Mre11-Rad50 Complex." Molecular Cell, vol. 64, no. 2, 2016, pp. 405-415.
Oh J, Al-Zain A, Cannavo E, et al. Xrs2 Dependent and Independent Functions of the Mre11-Rad50 Complex. Mol Cell. 2016;64(2):405-415.
Oh, J., Al-Zain, A., Cannavo, E., Cejka, P., & Symington, L. S. (2016). Xrs2 Dependent and Independent Functions of the Mre11-Rad50 Complex. Molecular Cell, 64(2), 405-415. https://doi.org/10.1016/j.molcel.2016.09.011
Oh J, et al. Xrs2 Dependent and Independent Functions of the Mre11-Rad50 Complex. Mol Cell. 2016 10 20;64(2):405-415. PubMed PMID: 27746018.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Xrs2 Dependent and Independent Functions of the Mre11-Rad50 Complex. AU - Oh,Julyun, AU - Al-Zain,Amr, AU - Cannavo,Elda, AU - Cejka,Petr, AU - Symington,Lorraine S, Y1 - 2016/10/13/ PY - 2016/04/28/received PY - 2016/07/22/revised PY - 2016/09/08/accepted PY - 2016/10/22/pubmed PY - 2017/9/9/medline PY - 2016/10/18/entrez KW - DNA repair KW - Mre11 KW - Rad50 KW - Sae2 KW - Xrs2 KW - end resection KW - homologous recombination SP - 405 EP - 415 JF - Molecular cell JO - Mol Cell VL - 64 IS - 2 N2 - The Mre11-Rad50-Xrs2/Nbs1 (MRX/N) complex orchestrates the cellular response to DSBs through its structural, enzymatic, and signaling roles. Xrs2/Nbs1 is essential for nuclear translocation of Mre11, but its role as a component of the complex is not well defined. Here, we demonstrate that nuclear localization of Mre11 (Mre11-NLS) is able to bypass several functions of Xrs2, including DNA end resection, meiosis, hairpin resolution, and cellular resistance to clastogens. Using purified components, we show that the MR complex has equivalent activity to MRX in cleavage of protein-blocked DNA ends. Although Xrs2 physically interacts with Sae2, we found that end resection in its absence remains Sae2 dependent in vivo and in vitro. MRE11-NLS was unable to rescue the xrs2Δ defects in Tel1/ATM kinase signaling and non-homologous end joining, consistent with the role of Xrs2 as a chaperone and adaptor protein coordinating interactions between the MR complex and other repair proteins. SN - 1097-4164 UR - https://www.unboundmedicine.com/medline/citation/27746018/Xrs2_Dependent_and_Independent_Functions_of_the_Mre11_Rad50_Complex_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1097-2765(16)30560-3 DB - PRIME DP - Unbound Medicine ER -