Chapter category: Aging
Replicative Senescence, Telomeres and Werner’s Syndrome
Molecular Mechanisms of Werner's Syndrome
Edited by: Michel LebelISBN: 0-306-48233-9
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Chapter authors:
Richard G.A. Faragher
Werner’s syndrome (WS) is studied as a model of accelerated aging and results from mutations in a recQ helicase (WRN). WS fibroblasts show a mutator phenotype (producing large DNA deletions), replication fork stalling, increased rates of mean telomeric loss and accelerated replicative senescence. If Werner’s syndrome is to be of value as a model disease for the study of human aging, it is necessary to determine which of these features is relevant to the normal process and in what way. This requires that the biology of the disease be placed in the wider context of mechanisms believed to contribute to the normal aging process. The replicative senescence of somatic cells has been proposed as one such candidate mechanism for the aging of mitotic tissue. However, not all mitotic tissues are affected in Werner’s syndrome. Does this apparent paradox indicate that Werner’s syndrome is a poor model for aging or that replicative senescence is an unsatisfactory mechanism for it in many tissues? These questions are discussed with reference to the manner in which senescent cells are believed to contribute to the aging process and the ways in which cells may count divisions. Perhaps unexpectedly, the available data suggest that accelerated senescence should not be observed in all mitotic WS cell types.
Additional chapters from this book:
Replicative Senescence, Telomeres and Werner’s Syndrome
Richard G.A. Faragher
Werner’s syndrome (WS) is studied as a model of accelerated aging and results from mutations in a recQ helicase (WRN). WS fibroblasts show a mutator phenotype (producing large DNA deletions), replic...
Proposed Biological Functions for the Werner Syndrome Protein in DNA Metabolism
Patricia L. Opresko, Jeanine A. Harrigan, Wen-Hsing Cheng, Robert M. Brosh, Jr. and Vilhelm A. Bohr
Werner syndrome is a premature aging disease that is characterized by genomic instability. The gene defective in Werner syndrome encodes a protein with helicase and exonuclease activities. This chap...
Proteins That Interact with the Werner Syndrome Gene Product
Dana Branzei and Takemi Enomoto
Werner syndrome is an autosomal recessive disorder characterized by premature onset of age-related diseases, increased cancer incidence, and genomic instability. Biochemical characterization has sho...
Clinical Aspects of Werner’s Syndrome: Its Natural History and the Genetics of the Disease
Makoto Goto
Werner’s syndrome, caused by a mutation in the WRN (or RecQ3) helicase gene, shows a variety of clinical and biochemical-aging phenotypes at an early stage of life followed by death at an average ag...
Yeast RecQ Helicases: Clues to DNA Repair, Genome Stability and Aging
Rozalyn M. Anderson and David A. Sinclair
The budding yeast Saccharomyces cerevisiae has been used as model for a wide range of cellular processes, including those related to the RecQ-associated progeroid disease, Werner’s syndrome (WS). In...
Biochemical Characterization of the Werner Syndrome DNA Helicase—Exonuclease
Michael Fry
The positional cloning in 1996 of WRN, the human gene defective in Werner syndrome (WS), launched an explosive experimental activity that culminated in the expression, purification and comprehensive c...
Biochemical Roles of RecQ Helicases
Payam Mohaghegh and Ian D. Hickson
The RecQ family of DNA helicases appears to influence DNA repair, replication and/or homologous recombination pathways. In humans, a defect in the RecQ family helicases encoded by the BLM, WRN a...
Sensitivity of Werner's Syndrome Cells to DNA Damaging Agents: Insights into the Biological Functions of the Werner Protein
Adayabalam S. Balajee and Fabrizio Palitti
Werner’s syndrome (WS) is a human autosomal recessive disorder characterized by many symptoms of accelerated aging. The gene responsible for Werner’s syndrome (WRN) has been cloned and the protein has...
Potential Function of the Werner's Syndrome Homologue in the African Clawed Frog and the Mouse
Michel Lebel and Philip Leder
After the discovery of the gene responsible for WS in the human, genes with high homology to WRN were found in the mouse Mus musculus and the African clawed frog Xenopus laevis genome. These lab...
