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)

Fine analysis of DNA damage and repair at the subgenomic level has indicated a microheterogeneity of DNA repair in mammalian cells, including human. In addition to the well established Southern hybridization-based approach to investigate gene-specific DNA damage and repair, alternative methods utilizing the sensitivity of PCR have been evaluated. The latter technique has relied on decreased PCR amplification due to damage in template DNA. We have developed a novel quantitative assay combining the selective recovery of DNA damage containing genomic fragments with the PCR amplification. DNA isolated from 7,8-dihydroxy-anti-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (anti-BPDE) treated human skin fibroblasts was immunoprecipitated with polyclonal antibody BP-1. Recovered target sequences were amplified by PCR using primers encompassing a 149 bp target region around codon 12 of the H-ras proto-oncogene. Quantitative DNA damage specific response was observed with nanogram amounts of genomic DNA. This approach allowed analysis of the initial DNA damage at a level less than 1 anti-BPDE adduct per 6.4 kbp ras gene fragment. Repair proficient GM637 cells exposed to 2 microM anti-BPDE showed a faster removal of the adducts from the H-ras gene segment than from the genome overall. Gene-specific repair was not apparent in GM4429 xeroderma pigmentosum (complementation group A) cells. The established technique could be extended to the quantitative measurement of the repair of diverse DNA base lesions in any genomic region of known sequence.
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PMID:Assessment of DNA damage and repair in specific genomic regions by quantitative immuno-coupled PCR. 803 63

Defective mismatch repair has recently been implicated as the major contributor towards the mutator phenotype observed in tumour cell lines derived from patients diagnosed with hereditary non-polyposis colon cancer (HNPCC). Cell lines from other cancer-prone syndromes, such as xeroderma pigmentosum, have been found to be defective in nucleotide excision repair of damaged bases. Some genetic complementation groups are defective specifically in transcription-coupled excision repair, although this type of repair defect has not been associated with cancer proneness. Mechanisms contributing to the high incidence of activating point mutations in oncogenes (such as H-ras codon 12) are not understood. It is possible that novel mechanisms of misrepair or misreplication occur at these sites in addition to the above DNA repair mechanisms. In this study, we have compared the rate of strand-directed mismatch repair of four mispairs (G:A, A:C, T:C and G:T) at the H-ras codon 12, middle G:C position. Our results indicate that, although this location is not a 'hot spot' for bacterial mismatch repair, it is a 'hot spot' for decreased repair of specific mismatched bases within NIH 3T3 cells. NIH 3T3, unlike Escherichia coli, have an extremely low repair rate of the G:A mispair (35%), as well as the A:C mispair (58%) at this location. NIH 3T3 also have a moderately low repair rate of the T:C mispair (80%) at the codon 12 location. Conversely, NIH 3T3 repair of G:T (100%) is comparable to E. coli repair (94%) of this mismatch. These results demonstrate that a mismatch containing an incorrect adenine on either strand at the H-ras codon 12 middle base pair location is most likely to undergo a mutational event in NIH 3T3 cells. Conversely, a mismatch containing an incorrect thymine in the transcribed strand is least likely to undergo a mutational event.
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PMID:Site- and strand-specific mismatch repair of human H-ras genomic DNA in a mammalian cell line. 923 Feb 73

We investigated the association of urinary bladder cancer with genetic polymorphisms in the xeroderma pigmentosum complementation group C (XPC), group D (XPD) and group G (XPG), X-ray repair cross-complementing group 1 (XRCC1) and group 3 (XRCC3), Nijmegen breakage syndrome 1 (NBS1), cyclin D1, methylene-tetrahydrofolate reductase (MTHFR), NAD(P)H dehydrogenase quinone 1 (NQO1), H-ras and glutathione S-transferase theta 1 (GSTT1) genes. Bladder cancer patients from the different hospitals in Stockholm County Council area and matching controls were genotyped for different polymorphisms. The frequency of the variant allele for A/C polymorphism in exon 15 of the XPC gene was significantly higher in the bladder cancer cases than in the controls (OR 1.49, 95% CI 1.16-1.92, P = 0.001). The variant allele homozygote genotype for the T/C polymorphism in exon 1 of the H-ras gene was associated with a decreased risk for bladder cancer (OR 0.12, 95% CI 0.02-0.67, P = 0.006). The variant allele genotypes for the single nucleotide polymorphisms (SNPs) in DNA repair genes, XPG and NBS1, showed a marginal association with the occurrence of bladder cancer (OR 0.38, 95% CI 0.15-0.94, P = 0.03 and OR 1.64, 95% CI 0.92-2.90, P = 0.09, respectively). We also report a positive correlation between the null homozygote of GSTT1 with the risk of bladder cancer (OR 2.54, 95% CI 1.32-4.98, P = 0.003). For other polymorphisms included in this study, NBS1 Glu185Gln, XPD Lys751Gln, XPG Asp1104His, XRCC1 Arg399Gln, XRCC3 Thr241Met, cyclin D1 Pro242Pro, MTHFR Ala222Val and Glu429Ala, NQO1 Arg139Trp and Pro187Ser, no significant differences for genotype distributions and allele frequencies between the bladder cancer cases and the controls were observed in the present study.
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PMID:Polymorphisms in DNA repair and metabolic genes in bladder cancer. 1468 16