A (6-4) Photolyase Model: Repair of DNA (6-4) Lesions Requires a Reduced and Deprotonated Flavin

✍ Scribed by Michaela K. Cichon; Simone Arnold; Thomas Carell

• Book ID: 101373799
• Publisher: John Wiley and Sons
• Year: 2002
• Tongue: English
• Weight: 124 KB
• Volume: 114
• Category: Article
• ISSN: 0044-8249
• DOI: 10.1002/1521-3757(20020301)114:5<793::aid-ange793>3.0.co;2-w

✦ Synopsis

Ultraviolet irradiation of cells causes the formation of a variety of DNA lesions with known mutagenic, carcinogenic, and lethal effects. The main UV lesions are cyclobutane ± pyrimidine dimers (CPD lesions) formed in a photochemically allowed [2p 2p] cycloaddition and (6-4) photoadducts; the latter are presumably more mutagenic. The highly mutagenic (6-4) lesions are believed to be formed in a Paterno ¬ -B¸chi reaction between two adjacent pyrimidines in the DNA duplex to give initially an oxetane intermediate, which rearranges above À 80 8C to the (6-4) photoadduct by a proton shift and a CÀO bond scission (Scheme 1). Both types of DNA lesions are repaired in many organisms by a special class of repair enzymes, namely DNA photolyases, which cleave both lesions back into the monomers in a lightdependent, single electron transfer based repair reaction. In the last decade, crystallographic, enzymatic, and model compound studies [11±14] showed that the photolyases, which are responsible for the repair of CPD lesions, contain a [5]