We therefore speculated that the WRN gene (encoding RECQL2, a DNA helicase), the germline mutation of which causes the progeroid disorder Werner syndrome, may be associated with breast tumorigenesis.
We therefore examined WRN, a 3'-->5' exonuclease and helicase mutated in Werner syndrome, a disorder characterized by aberrant telomere maintenance, premature aging, chromosomal rearrangements, and predisposition to malignancy.
We show that wild-type WRN protein physically associates with PCNA at physiological protein concentrations in normal cells, while no association is seen in cells from patients with WS.
We show here that lipodystrophy and extreme insulin resistance can also reveal the adult progeriaWerner syndrome linked to mutations in WRN, encoding a RecQ DNA helicase.
We review the spectrum of WS-associated WRN mutations, the organization and potential functions of the WRN protein, and potential mechanistic links between the loss of WRN function and pathogenesis of the WS clinical and cellular phenotypes.
We report on a familial case of atypical Werner syndrome (a progeroid syndrome with Werner syndrome phenotype but without typical RECQL2 mutation) presenting with acute ischemic cerebral disease or peripheral artery disease associated with diffuse atherosclerosis, attributable to transmission of a novel LMNA mutation.
We propose that transcriptional misregulation of downstream genes by the absence of WRN protein contributes to the variable premature aging phenotypes of WS.
We prepared several monoclonal antibodies (mAbs) specific for the NH2- and COOH-terminal regions of the DNA helicase (WRN helicase) responsible for Werner's syndrome known as a premature aging disease.
We have assessed the role of the WRN gene in transcription by analyzing the efficiency of basal transcription in WS lymphoblastoid cell lines that carry homozygous WRN mutations.
We demonstrate here that the expression of the mutated WRN gene that produces nonsense mRNAs remains at low levels, resulting in the preferential expression of the intact WRN gene in the WS microcell hybrids.
We considered cells from patients with Hutchinson-Gilford progeria syndrome (HGPS) with an altered nucleoskeletal protein; a mouse model of XFE progeroid syndrome caused by a deficiency of ERCC1-XPF DNA repair nuclease; and patients with Werner syndrome (WS) lacking a functional WRN exonuclease and helicase protein.
We conclude that, despite evidence of accelerated senescence in WS cells, there is no evidence that the absence of active WRN acts as a barrier to neoplastic transformation.
We asked whether spontaneous sarcomas, not known to be associated with WS, also harbor mutations or unreported single nucleotide polymorphisms (SNPs) in WRN.
To investigate whether the WRN gene affects the course of aging in non-Werner syndrome individuals, we performed association studies analyzing several single nucleotide polymorphisms (SNPs) in the WRN locus.