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Nucleic Acids Research Advance Access published online on November 5, 2009
Nucleic Acids Research, doi:10.1093/nar/gkp905
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© The Author(s) 2009. Published by Oxford University Press.
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.5/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Genome Integrity, Repair and Replication

The Mre11/Rad50/Nbs1 complex functions in resection-based DNA end joining in Xenopus laevis

Elaine M. Taylor1, Sophie M. Cecillon2, Antonio Bonis1, J. Ross Chapman2, Lawrence F. Povirk3 and Howard D. Lindsay1,*

1Divisions of Medicine and Biomedical and Life Sciences, School of Health and Medicine, Lancaster University, Bailrigg, Lancaster, LA1 4YQ, 2Genome Damage and Stability Centre, University of Sussex, Falmer, Brighton, BN1 9RQ, UK and 3Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, VA 23298-0035, USA

*To whom correspondence should be addressed. Tel: +44 1524 592058; Fax: +44 1524 593192; Email: h.lindsay{at}lancaster.ac.uk

Received June 25, 2009. Revised October 5, 2009. Accepted October 7, 2009.

The repair of DNA double-strand breaks (DSBs) is essential to maintain genomic integrity. In higher eukaryotes, DNA DSBs are predominantly repaired by non-homologous end joining (NHEJ), but DNA ends can also be joined by an alternative error-prone mechanism termed microhomology-mediated end joining (MMEJ). In MMEJ, the repair of DNA breaks is mediated by annealing at regions of microhomology and is always associated with deletions at the break site. In budding yeast, the Mre11/Rad5/Xrs2 complex has been demonstrated to play a role in both classical NHEJ and MMEJ, but the involvement of the analogous MRE11/RAD50/NBS1 (MRN) complex in end joining in higher eukaryotes is less certain. Here we demonstrate that in Xenopus laevis egg extracts, the MRN complex is not required for classical DNA-PK-dependent NHEJ. However, the XMRN complex is necessary for resection-based end joining of mismatched DNA ends. This XMRN-dependent end joining process is independent of the core NHEJ components Ku70 and DNA-PK, occurs with delayed kinetics relative to classical NHEJ and brings about repair at sites of microhomology. These data indicate a role for the X. laevis MRN complex in MMEJ.

Present address: J. Ross Chapman, Department of Zoology, Wellcome Trust and Cancer Research, UK Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK.

The authors wish it to be known that, in their opinion, the first two authors should be regarded as joint First Authors.


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