Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0043346 (xeroderma pigmentosum)
 2,924 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

DNA repair mechanisms usually consist of a complex network of enzymatic reactions catalyzed by a large family of mutually interacting gene products. Thus deficiency, alteration or low levels of a single enzyme and/or of auxiliary proteins might impair a repair process. There are several indications suggesting that some enzymes involved both in DNA replication and repair are less abundant if not completely absent in stationary and non replicating cells. Postmitotic brain cell does not replicate its genome and has lower levels of several DNA repair enzymes. This could impair the DNA repair capacity and render the nervous system prone to the accumulation of DNA lesions. Some human diseases clearly characterized by a DNA repair deficiency, such as xeroderma pigmentosum, ataxia-telangiectasia and Cockayne syndrome, show neurodegeneration as one of the main clinical and pathological features. On the other hand there is evidence that some diseases characterized by primary neuronal degeneration (such as amyotrophic lateral sclerosis and Alzheimer disease) may have alterations in the DNA repair systems as well. DNA repair thus appears important to maintain the functional integrity of the nervous system and an accumulation of DNA damages in neurons as a result of impaired DNA repair mechanisms may lead to neuronal degenerations.
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PMID:DNA repair mechanisms in neurological diseases: facts and hypotheses. 146 39

Experimental evidence implicates oxidative free radical reactions as central in the processes of neurodegenerative diseases. In particular, cellular interactions with the beta-amyloid protein have been linked to neuron cell death in Alzheimer's disease. Also, uncharacterized dimeric purine moieties have been detected in oxidized DNAs. It has been suggested that inadequate excision-repair of such products plays a functional role in the neurological degeneration observed in familial Alzheimer's disease, Down's syndrome, and xeroderma pigmentosum. Therefore, in order to obtain a reagent to monitor the presence of such products, the purine dimer 8-8-(2'-deoxyguanosyl)-2'-deoxyguanosine-5'-monophosphate was used as a hapten for elicitation of rabbit anti-purine dimer antiserum. This antiserum specifically recognizes various purified 8-8-bideoxyribonucleosides and 8-8-bideoxyribonucleotides. We found that DNA oxidized by the Fenton reaction is specifically recognized by this antiserum. This reagent can therefore be used to demonstrate formation and excision of DNA purine dimers. Moreover, incubation of cultured rat pheochromocytoma PC-12 cells with the beta-amyloid protein resulted in formation of these purine dimers in cellular DNA. These dimers were subsequently removed from cellular DNA. From these results we conclude that the free radicals generated by A beta cause oxidative DNA alterations including purine dimers. Deficient repair of this type of DNA damage might result in neural cell loss via apoptosis. Our findings suggest mechanisms for the roles of beta-amyloid and oxidative free radicals in neurodegenerative diseases and the role of DNA excision-repair in the prevention of lethal neurotoxicity.
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PMID:beta-Amyloid protein induces the formation of purine dimers in cellular DNA. 1125 22