Exposure to DNA-damaging agents triggers signal transduction pathways that are thought to play a role in maintenance of genomic stability. A key protein in the cellular processes of nucleotide excision repair, DNA recombination, and DNA double-strand break repair is the single-stranded DNA binding protein, RPA. We showed previously that the p34 subunit of RPA becomes hyperphosphorylated as a delayed response (4-8 h) to UV radiation (10-30 J/m(2)). Here we show that UV-induced RPA-p34 hyperphosphorylation depends on expression of ATM, the product of the gene mutated in the human genetic disorder ataxia telangiectasia (A-T). UV-induced RPA-p34 hyperphosphorylation was not observed in A-T cells, but this response was restored by ATM expression. Furthermore, purified ATM kinase phosphorylates the p34 subunit of RPA complex in vitro at many of the same sites that are phosphorylated in vivo after UV radiation. Induction of this DNA damage response was also dependent on DNA replication; inhibition of DNA replication by aphidicolin prevented induction of RPA-p34 hyperphosphorylation by UV radiation. We postulate that this pathway is triggered by the accumulation of aberrant DNA replication intermediates, resulting from DNA replication fork blockage by UV photoproducts. Further, we suggest that RPA-p34 is hyperphosphorylated as a participant in the recombinational postreplication repair of these replication products. Successful resolution of these replication intermediates reduces the accumulation of chromosomal aberrations that would otherwise occur as a consequence of UV radiation.

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Guarana (Paullinia cupana) is a popular herb native to the Amazon Basin and used extensively in soft drinks in Brazil, other Latin American countries, and more recently in the United States. Extracts derived from the dried seeds of guarana possess strong anti-platelet aggregatory properties. In this study, an active fraction containing this activity was purified and analyzed by high-performance liquid chromatography/mass spectrometry (HPLC/MS) techniques. It was noted that this fraction contains catechins, epicatechins, and their dimers, with a small amount of caffeine. It is suggested that complexes containing caffeine and catechins (and their dimers) might be responsible for anti-platelet aggregatory activity in guarana seeds and might offer health benefits towards decreasing risk of thrombosis and cardiovascular disease.

The effects of sucrose polyester (SPE) (a nonabsorbable mixture of hex-a, hepta,- and octa-fatty acid esters of sucrose with physical properties similar to those of common dietary fats) on fecal bile acid excretion and composition were assessed in 24 healthy, nonobese, normolipemic male volunteers, in a 40-day, inpatient, metabolic balance study. Isocaloric diets provided either 800, 300, or less than 50 mg of cholesterol/day (P/S ratios respectively 0.4, 1.0, and 1.5). After diet-only perids of 10 days (for the 800 and 300 mg cholesterol regimens), and 21 days (for the 50 mg diet), the diets were continued for 30 days, with addition of SPE to diets over three successive treatment periods of 10 days each, with 8, 16, and 35 g of liquid SPE/day, or 15, 30, and 50 g SPE/day in a SPE-hydrogenated palm oil mix. On both the liquid SPE and SPE-hydrogenated palm oil mix, there were no significant changes in fecal bile acid excretion as a function of dietary SPE, at any level of cholesterol intake, P > 0.1. In most subjects SPE changed fecal bile acid composition; lithocholic acid was decreased, and in most instances this was accompanied by the appearance and increase in chenodeoxycholic acid. In one subject, both deoxycholic and 3 beta, 12 alpha-dihydroxycholanic acid were reduced, with an accompanying increase in cholic acid. The hypocholesterolemic effect of SPE appears to be mediated through its reduction of intestinal absorption of cholesterol, not through effects on bile acid excretion.