Functional role of the Werner syndrome RecQ helicase in human fibroblasts

Kiranjit Dhillon 1 Julia Sidorova 1 Yannick Saintigny 1, * Martin Poot 1 Katherine Gollahon 1 Peter Rabinovitch 1 Raymond Monnat 1
* Corresponding author
1 University of Washington [Seattle]
Abstract : 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.
Keywords : RecQ helicase Werner syndrome DNA repair DNA replication homologous recombination premature aging
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Journal articles
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https://hal-cea.archives-ouvertes.fr/cea-01938105
Contributor : Yannick Saintigny <>
Submitted on : Wednesday, November 28, 2018 - 2:37:58 PM
Last modification on : Thursday, November 29, 2018 - 12:01:50 PM

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Kiranjit Dhillon, Julia Sidorova, Yannick Saintigny, Martin Poot, Katherine Gollahon, et al.. Functional role of the Werner syndrome RecQ helicase in human fibroblasts. Aging Cell, Wiley Open Access, 2007, 6 (1), pp.53 - 61. ⟨10.1111/j.1474-9726.2006.00260.x⟩. ⟨cea-01938105⟩

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