Insights into Light‐driven DNA Repair by Photolyases: Challenges and Opportunities for Electronic Structure Theory1. (5th January 2017)

• Record Type: Journal Article
• Authors: Faraji, Shirin; Dreuw, Andreas
• Is Part Of: Photochemistry and photobiology. Volume 93:Number 1(2017)
• Page Start: 37
• Page End: 50
• Publication Date: 2017-01-05
• Subjects: Photochemistry -- Periodicals; Light -- Physiological effect -- Periodicals; 541.35
• DOI: 10.1111/php.12679
• Languages: English
• ISSNs: 0031-8655

Abstract

Abstract: Ultraviolet radiation causes two of the most abundant mutagenic and cytotoxic DNA lesions: cyclobutane pyrimidine dimers and 6‐4 photoproducts. (6‐4) Photolyases are light‐activated enzymes that selectively bind to DNA and trigger repair of mutagenic 6‐4 photoproducts via photoinduced electron transfer from flavin adenine dinucleotide anion (FADH − ) to the lesion triggering repair. This review provides an overview of the sequential steps of the repair process, that is light absorption and resonance energy transfer, photoinduced electron transfer and electron‐induced splitting mechanisms, with an emphasis on the role of theory and computation. In addition, theoretical calculations and physical properties that can be used to classify specific mechanism are discussed in an effort to trace the fundamental aspects of each individual step and assist the interpretation of experimental data. The current challenges and suggested future directions are outlined for each step, concluding with a view on the future. Abstract : This review provides an overview of the sequential steps of the repair process of 6‐4 photoproducts, highlighting the interplay between theory and experiment. Theoretical studies revealed that photoinduced electron generation occurs via an ICD process. Combined experimental and theoretical studies have demonstrated that electron‐induced splitting mechanism involves a proton‐coupled electron transfer from protonated His365 to N3′ of the 3′‐T making the concerted transfer of the OH group from C5 to C4′ via an oxetane‐like transition state feasible. The experimental spectroscopic signature of the detected 6‐4PP intermediate is assigned theoretically to a specific molecular structure identifying the acting molecular mechanism.