Article abstract
Nature Structural & Molecular Biology 14, 639 - 646 (2007)
Published online: 24 June 2007 | doi:10.1038/nsmb1261
Role of Dnl4–Lif1 in nonhomologous end-joining repair complex assembly and suppression of homologous recombination
Yu Zhang1,4, Melissa L Hefferin2,4, Ling Chen2,4, Eun Yong Shim1, Hui-Min Tseng2, Youngho Kwon3, Patrick Sung3, Sang Eun Lee1 & Alan E Tomkinson2
Abstract
Nonhomologous end joining (NHEJ) eliminates DNA double-strand breaks (DSBs) in bacteria and eukaryotes. In Saccharomyces cerevisiae, there are pairwise physical interactions among the core complexes of the NHEJ pathway, namely Yku70–Yku80 (Ku), Dnl4–Lif1 and Mre11–Rad50–Xrs2 (MRX). However, MRX also has a key role in the repair of DSBs by homologous recombination (HR). Here we have examined the assembly of NHEJ complexes at DSBs biochemically and by chromatin immunoprecipitation. Ku first binds to the DNA end and then recruits Dnl4–Lif1. Notably, Dnl4–Lif1 stabilizes the binding of Ku to in vivo DSBs. Ku and Dnl4–Lif1 not only initiate formation of the nucleoprotein NHEJ complex but also attenuate HR by inhibiting DNA end resection. Therefore, Dnl4–Lif1 plays an important part in determining repair pathway choice by participating at an early stage of DSB engagement in addition to providing the DNA ligase activity that completes NHEJ.
- Department of Molecular Medicine, Institute of Biotechnology, The University of Texas Health Science Center at San Antonio, Texas 78245, USA.
- Radiation Research Laboratory, Department of Radiation Oncology and the Marlene and Stewart Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, Maryland 21201-1509, USA.
- Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut 06520-8024, USA.
- These authors contributed equally to this work.
Correspondence to: Sang Eun Lee1 e-mail: lees4@uthscsa.edu
Correspondence to: Alan E Tomkinson2 e-mail: atomkinson@som.umaryland.edu
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