Werner syndrome: a molecular genetic hypothesis.
On the basis of clinical and experimental observations, we postulate that the primary genetic abnormality in Werner syndrome (WS) is mutation in a gene encoding a trans-acting factor that normally represses a second genetic locus or its product, an inhibitor of DNA synthesis elaborated when cells reach the end of their replicative life span. The result is early derepression of this second locus, leading to reduced initiation of DNA synthesis and premature replicative senescence. This hypothesis and its corollaries provide a heuristic model for decisive experiments.
Department of Medicine, University of Arkansas for Medical Sciences, Little Rock.
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S
Goldstein
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S
Murano
R J
RJ
Shmookler Reis
D004247:DNA / Q000096:biosynthesis / Q000235:genetics; D005809:Genes, Regulator; D006801:Humans; D009154:Mutation; D014898:Werner Syndrome / Q000235:genetics*
D004247:DNA