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 in man can be described in general terms, but details are still obscure. Excision repair of base damage has a general similarity to the mechanism of the bacterial uvr ABC exonuclease, but the individual roles of at least 15 genes that regulate mammalian excision repair are as yet unknown. The differential repair of specific regions of DNA and of specific genes is highlighted by the clustered mode of repair characteristic of xeroderma pigmentosum group C and by the rapid repair of the dihydrofolate reductase gene. Cloning of genes that specify repair in man is proceeding slowly, in part, because of confusion by genes that produce only partial correction or nonspecific changes in sensitivity and by phenotypic reversion. In human cells, DNA damage-inducible genes are recognized that may overlap the spectra of other stress-induced proteins, but the relationship of these to any error-prone or recA-like system is unknown and unlikely. Four diseases, xeroderma pigmentosum, ataxia telangiectasia, Cockayne syndrome, and Fanconi anemia, have well-documented and significantly increased sensitivities to DNA-damaging agents, and each has recognizable though complex abnormalities in processing DNA damage. In addition, a wide variety of diseases and cellular processes have been ascribed to an association with DNA damage and repair, but the accuracy and significance of these associations are hard to identify.
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PMID:DNA repair in man. 265 41

Recent studies by others have shown that the endonuclease complex coded for by the uvrA, uvrB and uvrC genes of Escherichia coli (UVR ABC excision nuclease) can incise DNA containing a variety of 'bulk-type' lesions, such as those resulting from u.v. light, (+/-)-7 alpha,8 beta-dihydroxy-9 alpha,10 alpha-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (anti-BPDE), and N-acetoxy-2-acetylaminofluorene. Using partially purified UVR ABC excision nuclease, we have quantitated the number of endonuclease sensitive sites (ESS) in purified DNA isolated from human fibroblasts treated with u.v. light or BPDE. The number of ESS/10(8) daltons of DNA were calculated from the number average mol. wt. of the DNA as determined by sedimentation in alkaline sucrose gradients. The number of endonuclease sites increased linearly with increasing doses of either u.v. light or BPDE. The UVR ABC excision nuclease was able to incise a majority of the BPDE-DNA adducts. Xeroderma pigmentosum fibroblasts, complementation group A (XP12BE) had 20-25% more ESS at each dose than the BPDE-treated normal (HSBP) cells. Cells treated with 4 microM BPDE and allowed 12 h of incubation to perform excision repair showed removal of 60% of the initial number of ESS from HSBP DNA and 40% of the ESS from XP-A DNA. Beyond 12 h XP12BE cells lost no additional ESS while HSBP cells continued to lose ESS, although at a slower rate, until at 48 h only 22% of the initial ESS remained. In cells treated with 10 J/m2 of u.v. light, the UVR ABC excision nuclease detected 60% of the sites recognized by the pyridimine dimer specific Micrococcus luteus glycosylase/apyrimidinic endonuclease. These results demonstrate the potential use of the UVR ABC excision nuclease in a quantitative assay for determining the number of carcinogen-induced lesions in human DNA.
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PMID:Quantitation of carcinogen-induced DNA damage and repair in human cells with the UVR ABC excision nuclease from Escherichia coli. 308 Feb 55