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DNA Repair (Amst). 2013 Jun 1;12(6):414-21. doi: 10.1016/j.dnarep.2013.03.004. Epub 2013 Apr 11.

Functional deficit associated with a missense Werner syndrome mutation.

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1
Laboratory of Molecular Gerontology, National Institute on Aging, 251 Bayview Blvd, Suite 100, Baltimore, MD 21224, USA.

Abstract

Werner syndrome (WS) is a rare autosomal recessive disorder caused by mutations in the WRN gene. WRN helicase, a member of the RecQ helicase family, is involved in various DNA metabolic pathways including DNA replication, recombination, DNA repair and telomere maintenance. In this study, we have characterized the G574R missense mutation, which was recently identified in a WS patient. Our biochemical experiments with purified mutant recombinant WRN protein showed that the G574R mutation inhibits ATP binding, and thereby leads to significant decrease in helicase activity. Exonuclease activity of the mutant protein was not significantly affected, whereas its single strand DNA annealing activity was higher than that of wild type. Deficiency in the helicase activity of the mutant may cause defects in replication and other DNA metabolic processes, which in turn could be responsible for the Werner syndrome phenotype in the patient. In contrast to the usual appearance of WS, the G574R patient has normal stature. Thus the short stature normally associated with WS may not be due to helicase deficiency.

PMID:
23583337
PMCID:
PMC3660515
DOI:
10.1016/j.dnarep.2013.03.004
[Indexed for MEDLINE]
Free PMC Article
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