Skip Navigation


Nucleic Acids Research Advance Access originally published online on March 6, 2009
Nucleic Acids Research 2009 37(8):2645-2657; doi:10.1093/nar/gkp147
This Article
Right arrow Full Text Freely available
Right arrow Print PDF (6191K) Freely available
Right arrow Screen PDF (791K) Freely available
Right arrow Supplementary Data
Right arrowOA All Versions of this Article:
37/8/2645    most recent
gkp147v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Commercial Re-use Guidelines
for Open Access NAR Content
Google Scholar
Right arrow Articles by Zheng, L.
Right arrow Articles by Janscak, P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Zheng, L.
Right arrow Articles by Janscak, P.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Nucleic Acids Research, 2009, Vol. 37, No. 8 2645-2657
© 2009 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Nucleic Acid Enzymes

MRE11 complex links RECQ5 helicase to sites of DNA damage

Lu Zheng1, Radhakrishnan Kanagaraj1, Boris Mihaljevic1, Sybille Schwendener1, Alessandro A. Sartori1, Bertran Gerrits2, Igor Shevelev3 and Pavel Janscak1,3,*

1Institute of Molecular Cancer Research, University of Zurich, 2Functional Genomics Center Zurich, UZH/ETH Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland and 3Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Videnska 1083, 14300 Prague, Czech Republic

*To whom correspondence should be addressed. Tel: +41 44 635 3470; Fax: +41 44 635 3484; Email: pjanscak{at}imcr.uzh.ch

Received December 22, 2008. Revised February 19, 2009. Accepted February 19, 2009.

RECQ5 DNA helicase suppresses homologous recombination (HR) possibly through disruption of RAD51 filaments. Here, we show that RECQ5 is constitutively associated with the MRE11–RAD50–NBS1 (MRN) complex, a primary sensor of DNA double-strand breaks (DSBs) that promotes DSB repair and regulates DNA damage signaling via activation of the ATM kinase. Experiments with purified proteins indicated that RECQ5 interacts with the MRN complex through both MRE11 and NBS1. Functional assays revealed that RECQ5 specifically inhibited the 3'->5' exonuclease activity of MRE11, while MRN had no effect on the helicase activity of RECQ5. At the cellular level, we observed that the MRN complex was required for the recruitment of RECQ5 to sites of DNA damage. Accumulation of RECQ5 at DSBs was neither dependent on MDC1 that mediates binding of MRN to DSB-flanking chromatin nor on CtIP that acts in conjunction with MRN to promote resection of DSBs for repair by HR. Collectively, these data suggest that the MRN complex recruits RECQ5 to sites of DNA damage to regulate DNA repair.

Present address: Lu Zheng, Department of Chemistry, University of Basel, Spitalstrasse 51, CH-4056 Basel, Switzerland

The authors wish it to be known that, in their opinion, the second and third authors should be regarded as joint second authors.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.