Disease relevance of Werner Syndrome

• Mutants for sgs1, the yeast homolog of the Werner's syndrome gene, accumulate ERCs more rapidly, leading to premature aging and a shorter life span [1].
• Bloom's syndrome (BS) and Werner's syndrome (WS) are genetic disorders in which an increased rate of chromosomal aberration is detected [2].
• Mutations in genes with consensus helicase homology have been found in cancer-prone syndromes such as xeroderma pigmentosum and Bloom syndrome as well as Werner's syndrome, in which patients age prematurely, and the X-linked mental retardation with alpha-thalassemia syndrome, ATR-X [3].
• The yeast Saccharomyces cerevisiae Sgs1 protein is a member of a family of DNA helicases that include the Escherichia coli RecQ protein and the products of human Bloom's syndrome and Werner's syndrome genes [4].
• OBJECTIVE: Studies were made on the abnormality of glucose and lipid metabolism and its cause in four patients with Werner's syndrome to infer the reason for accelerated atherogenesis in this syndrome [5].

High impact information on Werner Syndrome

• The capacity of enforced telomerase expression to rescue premature senescence of cultured cells from individuals with Werner syndrome and the lack of a disease phenotype in Wrn-deficient mice with long telomeres implicate telomere attrition in the pathogenesis of Werner syndrome [6].
• Telomerase prevents the accelerated cell ageing of Werner syndrome fibroblasts [7].
• In animals, genes that are homologous to RecQ protein, such as the human genes for Bloom's syndrome and Werner's syndrome, may also function in PTGS [8].
• The data suggest that failure of one or more PDGF-mediated pathways in Werner's syndrome cells may contribute to the phenotypic expression of the disorder [9].
• Congestive cardiomyopathy in Werner's syndrome [10].

Chemical compound and disease context of Werner Syndrome

• 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 [11].
• Troglitazone ameliorates insulin resistance in patients with Werner's syndrome [12].
• Fibroblasts derived from patients with Werner's syndrome (WS) were incubated with radioactive sulfate to study the incorporation of 35S into glycosaminoglycans (GAGs) [13].
• CONCLUSIONS: These results show a lack of caffeine effect in Werner's syndrome cells, suggesting an involvement of the Werner's syndrome protein in the signal transduction pathway by which caffeine could override the DNA damage induced G2 checkpoint [14].
• RESULTS: Hydroxyurea post-treatment potentiated the X-ray-induced aberration levels both in the normal and Werner's syndrome (KO375 and DJG) cell lines; in contrast caffeine was only effective in the normal cell line [14].

Biological context of Werner Syndrome

• The requirement of mouse DNA topoisomerase IIIalpha during early embryogenesis is discussed in terms of its plausible role in chromosome replication and its interaction with the RecQ/SGS1 family of DNA helicases, whose members include the Bloom's syndrome and the Werner's syndrome gene products [15].
• The regulation of Werner's syndrome gene (WRN) expression was studied by characterizing the cis-regulatory elements in the promoter region and the trans-activating factors that bind to them [16].
• Recent data suggest that the yeast enzyme Sgs1p, as well as two human homologues, which are encoded by the Bloom's and Werner's syndrome genes, function during DNA replication and possibly in a replication checkpoint specific to S phase [17].
• The Werner's syndrome gene (WRN) recently cloned, encodes for an helicase and therefore plays a role in DNA metabolism and DNA repair [18].
• The correlation between mutations in the Werner's syndrome (WRN) gene and the haplotypes of surrounding markers was studied in Japanese patients [19].

Anatomical context of Werner Syndrome

• Impaired S-phase transit of Werner syndrome cells expressed in lymphoblastoid cell lines [20].
• Normal thermostability of hypoxanthine guanine phosphoribosyltransferase in erythrocytes from Werner's syndrome patients [21].
• These results indicate that in monocyte-derived macrophages of patients with Werner's syndrome, the uptake, lysosomal hydrolysis, and re-esterification of free cholesterol are enhanced with no change in the receptor binding of acetylated LDL [22].
• Binding and tyrosine kinase activities of the insulin receptor on Epstein-Barr virus transformed lymphocytes from patients with Werner's syndrome [23].

Gene context of Werner Syndrome

• All of these phenotypic consequences of loss of Top3p function are at least partially suppressed by deletion of SGS1, the yeast homologue of the human Bloom's and Werner's syndrome genes [24].
• The SGS1 of Saccharomyces cerevisiae is a homologue of the Bloom's syndrome and Werner's syndrome genes [25].
• Characterisation of the interaction between WRN, the helicase/exonuclease defective in progeroid Werner's syndrome, and an essential replication factor, PCNA [26].
• Close linkage of the gene for Werner's syndrome to ANK1 and D8S87 on the short arm of chromosome 8 [27].
• LMNA mutations in atypical Werner's syndrome [28].

References