Telomeric abnormalities caused by loss of function of the RecQ helicase WRN are linked to the multiple premature ageing phenotypes that characterize Werner syndrome. Here we examine WRN's role in telomeric maintenance, by comparing its action on a variety of DNA structures without or with telomeric sequences. Our results show that WRN clearly prefers to act on strand invasion intermediates in a manner that favours strand invasion and exchange. Moreover, WRN unwinding of these recombination structures is further enhanced when the invading strand contains at least three G-rich single-stranded telomeric repeats. These selectivities are most pronounced at NaCl concentrations within the reported intranuclear monovalent cation concentration range, and are partly conferred by WRN's C-terminal region. Importantly, WRN's specificity for the G-rich telomeric sequence within this precise structural context is particularly relevant to telomere metabolism and strongly suggests a physiological role in telomeric recombination processes, including T-loop dynamics.

Document Type


Publication Date


Notes/Citation Information

Published in Nature Communications, v. 6, article 8331, p. 1-13.

© 2015 Macmillan Publishers Limited. All rights reserved.

This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

Digital Object Identifier (DOI)


Funding Information

This work was supported by grant AG027258 from the National Institute of Aging to D.K.O. and A.M. and also in part by funds from the Intramural Program of the National Institute on Aging, National Institutes of Health. D.N.E. was supported in part by training grant T32ES007266 from the National Institute of Environmental Health Sciences. This research was also supported by the Biostatistics and Bioinformatics Shared Resource of the University of Kentucky Markey Cancer Center (P30CA177558).

ncomms9331-s1.pdf (1581 kB)
Supplementary Figures 1-7 and Supplementary Tables 1-2