DNA repair by photolyases

Abstract

Photolyases belong to the cryptochrome/photolyase protein family (CPF) which perform different functions such as DNA repair, circadian photoreceptor, and transcriptional regulation. Photolyase protein is a DNA repair enzyme that repairs UV-induced DNA damages of cyclobutane pyrimidine dimer (CPD) and pyrimidine-pyrimidone (6-4) photoproducts using blue-light as an energy source. This enzyme is a flavoprotein containing two chromophores: flavin adenine dinucleotide (FAD) as a cofactor and a photoantenna such as methenyltetrahydrofolate (MTHF). The FAD is essential for catalysis DNA repair. MTHF absorbs photons from the blue light spectrum and transfers energy to FAD to increase the repair efficiency of the enzyme. Phylogenetic analysis in which amino acid sequences of several hundreds of CPF members are used suggests that they form more classes than we have considered so far. In this chapter, we discussed structure-functions and reaction mechanisms of different classes of photolyases. Table of Contents 1. Introduction 2. Cryptochrome/Photolyase protein family 2.1 Cofactors of the Photolyases 2.2 The crystal structure of the photolyase 2.3 Reaction Mechanism of DNA repair Mediated by CPD Photolyase 2.4 Reaction mechanisms of DNA repair mediated by (6-4) and other classes of the photolyases 3. Conclusion 4. Acknowledgment 5.References

Formation and Recognition of UV-Induced DNA Damage within Genome Complexity

“…An essential repair pathway of photon-induced damage is the direct repair (DR) pathway, which, interestingly, depends on photon-triggered enzymes called photolyases (PLs) ( Figure 2 a) [ 41 , 42 ]. Photolyases perform the repair of photolesions by reverting the damage [ 42 ]. In other words, this repair pathway does not rely on de novo DNA synthesis.…”

“…PLs are structurally composed of an N-terminal dinucleotide binding domain and a C-terminal binding domain for the catalytic cofactor: flavin adenine dinucleotide (FAD) [ 42 , 47 ]. Besides FAD, many PLs also bind additional chromophore such as methenyltetrahydrofolate (MTHF) or 8-hydroxy-7,8-didemethyl-5-deazariboflavin (8-HDF) [ 42 , 47 ].…”

“…PLs are structurally composed of an N-terminal dinucleotide binding domain and a C-terminal binding domain for the catalytic cofactor: flavin adenine dinucleotide (FAD) [ 42 , 47 ]. Besides FAD, many PLs also bind additional chromophore such as methenyltetrahydrofolate (MTHF) or 8-hydroxy-7,8-didemethyl-5-deazariboflavin (8-HDF) [ 42 , 47 ]. The electrostatic surface potential map shows an accumulation of positively loaded residues flanking a cavity localized in the vicinity of the flavin cofactor [ 59 , 60 ].…”

“…Upon stable binding to the CPD or 6-4PP photolesions, the photolyase performs the “direct repair” reaction ( Figure 2 a). For this purpose, FAD and additional photo-antenna molecules collect energy through the absorption of a blue light spectrum photon [ 42 ]. The energy transfer generates excited FADH − • [ 42 ].…”

“…For this purpose, FAD and additional photo-antenna molecules collect energy through the absorption of a blue light spectrum photon [ 42 ]. The energy transfer generates excited FADH − • [ 42 ]. In the case of CPD photolyases, FADH − • donates an electron to the CPD to catalyze the reversal repair reaction by cleaving the C5-C5 and C6-C-6 bonds of the cyclobutane ring [ 42 , 48 ].…”