Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.7.7 (DNA polymerase)
 17,007 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The sequence specificity in the photoreaction (365 nm) of 6,4,4'-trimethylangelicin (TMA) with DNA fragments of the lac I gene of Escherichia coli was studied by using DNA sequencing methodology. In order to map the sites of TMA photoaddition, we took advantage of the (3'-5') exonuclease activity associated with T4 DNA polymerase, which is blocked by bulky adducts, such as furocoumarin photoadducts. A quantitative analysis of the sites of photoaddition is reported. TMA was demonstrated to photoreact with thymine and, to a lower extent, to cytosine. AT-rich sequences and TTT sites in a GC context are the most reactive sites towards TMA whereas TA, AT, CA, AC sites are weaker sites with similar reactivity. Cytosines in alternated CG sequences are also targets of TMA photobinding. We observed a less pronounced sequence specificity of TMA than that of other psoralen derivatives already studied (Sage and Moustacchi, 1987; Boyer et al., 1988). A comparison with other furocoumarins 4,4'-dimethylangelicin (4,4'-DMA), 4'-methylangelicin (4'-MA), angelicin, 4,5',8-trimethylpsoralen (TMP) and 8-methoxypsoralen (8-MOP) is also reported. The role of flanking sequence and consequently of the local conformation at the various sites of photoaddition is discussed. A preferential orientation of the TMA molecule during the intercalation in the dark is suggested. Hot alkali treatment of TMA-modified DNA did not reveal any DNA strand breakage due to photooxidized bases.
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PMID:Monofunctional angular furocoumarins: sequence specificity in DNA photobinding of 6,4,4'-trimethylangelicin and other angelicins. 276 83

Inorganic arsenic increases urinary bladder transitional cell carcinoma in humans. In F344 rats, dimethylarsinic acid (DMA[V]) increases transitional cell carcinoma. Arsenic-induced inhibition of DNA repair has been reported in cultured cell lines and in lymphocytes of arsenic-exposed humans, but it has not been studied in urinary bladder. Should inhibition of DNA damage repair in transitional epithelium occur, it may contribute to carcinogenesis or cocarcinogenesis. We investigated morphology and expression of DNA repair genes in F344 rat transitional cells following up to 100 ppm DMA(V) in drinking water for four weeks. Mitochondria were very sensitive to DMA(V), and swollen mitochondria appeared to be the main source of vacuoles in the transitional epithelium. Real-time reverse transcriptase polymerase chain reaction (Real-Time RT PCR) showed the mRNA levels of tested DNA repair genes, ataxia telangectasia mutant (ATM), X-ray repair cross-complementing group 1 (XRCC1), excision repair cross-complementing group 3/xeroderma pigmentosum B (ERCC3/XPB), and DNA polymerase beta (Polbeta), were not altered by DMA(V). These data suggested that either DMA(V) does not affect DNA repair in the bladder or DMA(V) affects DNA repair without affecting baseline mRNA levels of repair genes. The possibility remains that DMA(V) may lower damage-induced increases in repair gene expression or cause post-translational modification of repair enzymes.
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PMID:Dimethylarsinic acid in drinking water changed the morphology of urinary bladder but not the expression of DNA repair genes of bladder transitional epithelium in F344 rats. 1938 86