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)

Those pyrimidine dimers that are repaired in confluent xeroderma pigmentosum Group C cells are clustered together in the genome. Although the average level of repair in this complementation group is of the order of 25% of normal, this percentage represents normal levels of repair in one quarter of the genome and little repair in the remainder. The factors that regulate this clustering process have been investigated using inhibitors of the initial incision step of repair (novobiocin) and of the polymerization step (aphidicolin). Novobiocin at a concentration that permitted 30% of repair to continue reduced the clustering of mended sites only slightly. Aphidicolin, in contrast, at a concentration that permitted 30 to 60% of repair to continue caused the mended sites to be distributed randomly. The clustering of repair sites seen in xeroderma pigmentosum Group C cells, therefore, is produced by an excision repair mechanism in which an aphidicolin-sensitive DNA polymerase, presumably alpha, plays an important regulatory role in determining which damaged sites are mended.
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PMID:Relative importance of incision and polymerase activities in determining the distribution of damaged sites that are mended in xeroderma pigmentosum group C cells. 310 77

The data in this paper show that when the inhibition of growth is measured, xeroderma pigmentosum (XP) complementation groups A, G and D are very sensitive to 4-nitroquinoline-1-oxide (4NQO), whereas only XP groups G and D are very sensitive to 3-methyl-4NQO (3me4NQO). Cells belonging to XP-C group are not particularly sensitive to either agent. Thus there are different epistasis groups for the excision repair of DNA adducts induced by these agents as opposed to the repair of u.v. damage. DNA polymerase alpha is involved in the repair of 4NQO-induced lesions because aphidicolin blocks their repair. XP cells from all the above groups are defective to some extent in this repair. The degree of repair defectiveness follows that seen after u.v., with even the XP-C cell line used having reduced repair (despite the fact that the inhibition of growth by 4NQO in this cell line was not markedly different from normal). Aphidicolin did not induce breaks in the normal or XP cell lines exposed to 3me4NQO, thus the repair of lesions induced by 3me4NQO does not involve DNA polymerase alpha in any of the cell lines. Finally, catalase reduces the alkaline labile lesions induced by 4NQO, but not 3me4NQO, suggesting the latter agent does not induce substantial amounts of DNA damage by the generation of radicals.
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PMID:The response to DNA damage induced by 4-nitroquinoline-1-oxide or its 3-methyl derivative in xeroderma pigmentosum fibroblasts belonging to different complementation groups: evidence for different epistasis groups involved in the repair of large adducts in human DNA. 311 41

Aphidicolin, a specific inhibitor of the eucaryotic alpha polymerase, has been employed to study the role of this enzyme in repair of potentially lethal damage (PLD) induced by far u.v. (254 nm) radiation in normal and repair defective primary human fibroblasts. There is strong concentration dependent specific toxicity to cells treated with a fluence of 6 Jm-2 of far-u.v. radiation and incubated with aphidicolin for 2 days over the concentration range 0.0025-2.5 micrograms/ml. A similar effect is seen with a xeroderma pigmentosum (XP) variant (excision proficient) strain but there is no specific toxicity to u.v. irradiated excision deficient XP cells of complementation group A. Inactivation of irradiated excision proficient fibroblasts is rapid over the first 6 h of aphidicolin (1 microgram/ml) treatment but the reaction takes 2 days or longer to complete depending on the u.v. dose. These results demonstrate that the apparent uncoupling of excision repair seen previously by other investigators prevents repair of PLD and is lethal to the cells.
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PMID:Specific toxicity of aphidicolin to ultraviolet-irradiated excision proficient human skin fibroblasts. 640 55

Aphidicolin is a specific inhibitor of DNA polymerase alpha. Its influence of DNA repair has been studied in both normal and excision deficient xeroderma pigmentosum cells exposed to u.v. irradiation at 254 nm. Single strand DNA breaks accumulated in u.v. irradiated normal cells when the inhibitor was present. Such breaks were absent in both unirradiated normal cells and in u.v. irradiated excision efficient cells incubated with the compound. The data therefore indicate that aphidicolin prevents the rejoining of single strand breaks formed during the excision repair process and imply that DNA polymerase alpha is involved in the repair of DNA in human cells.
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PMID:Aphidicolin: an inhibitor of DNA repair in human fibroblasts. 679 60