Photolyase

Evolution

Photolyase is a phylogenetically old enzyme which is present and functional in many species, from the bacteria to the fungi to plants and to the animals. Photolyase is particularly important in repairing UV induced damage in plants. The photolyase mechanism is no longer working in humans and other placental mammals who instead rely on the less efficient nucleotide excision repair mechanism, although they do retain many cryptochromes. Freezing stress in the annual wheat Triticum aestivum and in its perennial relative Thinopyrum intermedium is accompanied by large increases in expression of DNA photolyases.

Photolyases are flavoproteins and contain two light-harvesting cofactors. Many photolyases have an N-terminal domain that binds a second cofactor. All photolyases contain the two-electron-reduced FADH⁻; they are divided into two main classes based on the second cofactor, which may be either the pterin methenyltetrahydrofolate (MTHF) in folate photolyases or the deazaflavin 8-hydroxy-7,8-didemethyl-5-deazariboflavin (8-HDF) in deazaflavin photolyases. Although only FAD is required for catalytic activity, the second cofactor significantly accelerates reaction rate in low-light conditions. The enzyme acts by electron transfer in which the reduced flavin FADH⁻ is activated by light energy and acts as an electron donor to break the pyrimidine dimer.

On the basis of sequence similarities DNA photolyases can be grouped into a few classes:

• Class 1 CPD photolyases are enzymes that process cyclobutane pyrimidine dimer (CPD) lesions from Gram-negative and Gram-positive bacteria, as well as the halophilic archaea Halobacterium halobium.
• Class 2 CPD photolyases also process CPD lesions. They are found in plants like the thale cress Arabidopsis thaliana and the rice.
• The plant and fungi cryptochromes are similar to Class 1 CPDs. They are blue light photoreceptors that mediate blue light-induced gene expression and modulation of circadian rhythms.
• Class 3 CPD lyases make up a sister group to the plant cryptochromes, which in turn are a sister group to class 1 CPDs.
• The Cry-DASH group are CPD lyases highly specific for single-stranded DNA. Members include Vibrio cholerae, X1Cry from Xenopus laevis, and AtCry3 from Arabidopsis thaliana. DASH was initially named after Drosophila, Arabidopsis, Synechocystis, and Human, four taxa initially thought to carry this family of lyases. The categorization has since changed. The "Cry" part of their name was due to initial assumptions that they were cryptochromes.
• Eukaryotic (6-4)DNA photolyases form a group with animal cryptochromes that control circadian rhythms. They are found in diverse species including Drosophila and humans. The cryptochromes have their own detailed grouping.
• Bacterial 6-4 lyases (InterPro: IPR007357), also known as the FeS-BCP group, form their own outgroup relative to all photolyases.

The non-class 2 branch of CPDs tend to be grouped into class 1 in some systems such as PRINTS (PR00147). Although the members of the smaller groups are agreed upon, the phylogeny can vary greatly among authors due to differences in methodology, leading to some confusion with authors who try to fit everything (sparing FeS-BCP) into a two-class classification. The cryptochromes form a polyphyletic group including photolyases that have lost their DNA repair activity and instead control circadian rhythms.

Application

Adding photolyase from a blue-green algae Anacystis nidulans, to HeLa cells partially reduced DNA damage from UVB exposure.

Human proteins containing this domain

Cryptochromes: CRY1; CRY2

Nomenclature

The systematic name of this enzyme class is deoxyribocyclobutadipyrimidine pyrimidine-lyase. Other names in common use include photoreactivating enzyme, DNA photolyase, DNA-photoreactivating enzyme, DNA cyclobutane dipyrimidine photolyase, DNA photolyase, deoxyribonucleic photolyase, deoxyribodipyrimidine photolyase, photolyase, PRE, PhrB photolyase, deoxyribonucleic cyclobutane dipyrimidine photolyase, phr A photolyase, dipyrimidine photolyase (photosensitive), and deoxyribonucleate pyrimidine dimer lyase (photosensitive). This enzyme belongs to the family of lyases, specifically in the "catch-all" class of carbon-carbon lyases.