Photoreactivation

Most DNA repair processes remove the damaged nucleotides and several adjacent residues, then replace the excised region using information encoded in the complementary (undamaged) strand. Two processes, however, directly change the damaged bases, rather than removing them. They are photoreactivation and the process catalyzed by O6-alkylguanine alkyltransferase

The enzyme responsible for photoreactivation is called photoreactivating enzyme or DNA photolyase. It repairs cyclobutane pyrimidine dimers in the presence of visible light. A wavelength of 370 nm is most effective. Photoreactivating enzyme binds to DNA, in a light-independent process, at the site of pyrimidine dimers. In the presence of visible-wavelength light, the bonds linking the pyrimidine rings are broken, after which the enzyme can dissociate in the dark.

Photoreactivating enzyme contains two chromophores. (A chromophore is a structural moiety that absorbs light of characteristic wavelengths.) One chromophore is flavin adenine dinucleotide in the reduced state, FADH-. The second chromophore in some photolyases is 5,10-methenyltetrahydrofolate and in others is 8-hydroxy-5-deazaflavin.

Mechanistic studies suggest a process akin to photosynthesis, with the second chromophore functioning as a light-harvesting factor, and FADH- functioning like the photochemical reaction center, translating light energy to facilitate the transfer of an electron to the dimer and breaking the pyrimidine-pyrimidine bonds by a free radical mechanism, as shown in Figure 25.10.

Photolyase has been detected in numerous eukaryotic systems, but recent evidence indicates that human cells do not contain an enzyme for photoreactivation.

See also: Pyrimidine Dimers, O6-Alkylguanine Alkytransferase, Types and Consequences of DNA Damage, Light Absorbing Pigments (from Chapter 17), Photochemistry (from Chapter 17), Photosystem Summary (from Chapter 17)

INTERNET LINKS:

> 1. DNA Repair

> 2. Optimum Color Range for UV Mutagenesis Repair (online paper)