title: Cockayne's syndrome fibroblasts are characterized by hypersensitivity to deoxyguanosine and abnormal DNA precursor pool metabolism in response to deoxyguanosine or ultraviolet light.
abstract: New cellular traits of Cockayne's syndrome (CS) associated with DNA precursor metabolism have been identified, namely, hypersensitivity to the toxicity of low concentrations of deoxyguanosine (dG) and abnormal changes in deoxyribonucleotide (dNTP) pools in response to dG or UV. dG treatment results in similar ribonucleotide pool changes in wild-type and CS cells, i.e., GTP levels increase at least twofold. However, the changes in the pool size of the purine deoxyribonucleotides are significantly different; in wild-type cells dATP and dGTP pools increase threefold, but remain unchanged in CS. The mechanism by which dG kills CS cells is not clear, but unlike the inherited purine nucleoside phosphorylase deficiency disease, the toxicity of dG is not due to the accumulation of dGTP and the consequent feedback inhibition of ribonucleotide reductase. UV induces different dNTP pool changes in CS and wild-type cells. In wild-type cells dTTP, dCTP, and dATP pools increase three- to fivefold within 4 h of irradiation, while the dGTP pool contracts. In CS cells, only the dGTP pool expands (four- to sixfold), while the other three contract. Each of these new phenotypic traits, together with UV sensitivity, is coordinately corrected in the complementing proliferating CSA x CSB hybrid cells.
authors: Department of Zoology, University of Cambridge, UK.
authors: S
authors: S
authors: Squires
authors: D J
authors: DJ
authors: Oates
authors: S D
authors: SD
authors: Bouffler
authors: R T
authors: RT
authors: Johnson
mesh_terms: D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000528:radiation effects; D002478:Cells, Cultured; D003057:Cockayne Syndrome / Q000235:genetics / Q000378:metabolism*; D016172:DNA Fingerprinting; D004260:DNA Repair; D003849:Deoxyguanosine / Q000633:toxicity*; D003854:Deoxyribonucleotides / Q000378:metabolism*; D006131:Growth Inhibitors; D006801:Humans; D014466:Ultraviolet Rays
chemical_list: D003854:Deoxyribonucleotides; D006131:Growth Inhibitors; D003849:Deoxyguanosine