tailieunhanh - Báo cáo khoa học: Interaction of selenium compounds with zinc finger proteins involved in DNA repair

As an essential element, selenium is present in enzymes from several families, including glutathione peroxidases, and is thought to exert anticarcinogenic properties. A remarkable feature of selenium consists of its ability to oxidize thiols under reducing conditions. Thus, one mode of action recently suggested is the oxidation of thiol groups of metal-lothionein, thereby providing zinc for essential reactions. However, tetrahedral zinc ion complexation to four thio-lates, similar to that found in metallothionein, is present in one of the major classes of transcription factors and other so-called zinc finger proteins. . | Eur. J. Biochem. 271 3190-3199 2004 FEBS 2004 doi Interaction of selenium compounds with zinc finger proteins involved in DNA repair Holaer Blessina1. Silke Kraus1 PhiliDD Heindl1. Wojciech Bal2 and Andrea Hartwia1 3 Institute of Food Chemistry and Toxicology University of Karlsruhe Germany 2Institute of Biochemistry and Biophysics Polish Academy of Sciences Warsaw Poland 3Institute of Food Technology and Food Chemistry Technical University Berlin Germany As an essential element selenium is present in enzymes from several families including glutathione peroxidases and is thought to exert anticarcinogenic properties. A remarkable feature of selenium consists of its ability to oxidize thiols under reducing conditions. Thus one mode of action recently suggested is the oxidation of thiol groups of metal-lothionein thereby providing zinc for essential reactions. However tetrahedral zinc ion complexation to four thiolates similar to that found in metallothionein is present in one of the major classes of transcription factors and other so-called zinc finger proteins. Within this study we investigated the effect of selenium compounds on the activity of the formamidopyrimidine-DNA glycosylase Fpg a zinc finger protein involved in base excision repair and on the DNA-binding capacity and integrity of xeroderma pigmentosum group A protein XPA a zinc finger protein essential for nucleotide excision repair. The reducible selenium compounds phenylseleninic acid phenylselenyl chloride selenocystine ebselen and 2-nitrophenylselenocyanate caused a concentration-dependent decrease of Fpg activity while no inhibition was detected with fully reduced selenomethionine methylselenocysteine or some sulfur-containing analogs. Furthermore reducible selenium compounds interfered with XPA-DNA binding and released zinc from the zinc finger motif XPAzf. Zinc release was even evident at high glutathione oxidised glutathine ratios prevailing under cellular .