These authors contributed equally to the work described here.
Functional role of the Werner syndrome RecQ helicase in human fibroblasts
Article first published online: 14 NOV 2006
Volume 6, Issue 1, pages 53–61, February 2007
How to Cite
Dhillon, K. K., Sidorova, J., Saintigny, Y., Poot, M., Gollahon, K., Rabinovitch, P. S. and Monnat, R. J. (2007), Functional role of the Werner syndrome RecQ helicase in human fibroblasts. Aging Cell, 6: 53–61. doi: 10.1111/j.1474-9726.2006.00260.x
- Issue published online: 14 NOV 2006
- Article first published online: 14 NOV 2006
- Accepted for publication 6 October 2006
- DNA repair;
- DNA replication;
- homologous recombination;
- premature aging;
- RecQ helicase;
- Werner syndrome
Werner syndrome is an autosomal recessive human genetic instability and cancer predisposition syndrome that also has features of premature aging. We focused on two questions related to Werner syndrome protein (WRN) function in human fibroblasts: Do WRN-deficient fibroblasts have a consistent cellular phenotype? What role does WRN play in the recovery from replication arrest? We identified consistent cell proliferation and DNA damage sensitivity defects in both primary and SV40-transformed fibroblasts from different Werner syndrome patients, and showed that these defects could be revealed by acute depletion of WRN protein. Mechanistic analysis of the role of WRN in recovery from replication arrest indicated that WRN acts to repair damage resulting from replication arrest, rather than to prevent the disruption or breakage of stalled replication forks. These results identify readily quantified cell phenotypes that result from WRN loss in human fibroblasts; delineate the impact of cell transformation on the expression of these phenotypes; and define a mechanistic role for WRN in the recovery from replication arrest.