A UV radiation induced thymine-thymine cyclobutane dimer (right) is the type ofDNA damage which is repaired by DNA photolyase. Note: The above diagram is incorrectly labelled as thymine as the structures lack 5-methyl groups.
Photolyases (EC4.1.99.3) areDNA repairenzymes that repair damage caused by exposure toultraviolet light. These enzymes requirevisible light (from the violet/blue end of the spectrum) both for their own activation[1] and for the actual DNA repair.[2] The DNA repair mechanism involving photolyases is called photoreactivation. They mainly convert pyrimidine dimers into a normal pair of pyrimidine bases. Photo reactivation, the firstDNA repair mechanism to be discovered, was described initially by Albert Kelner in 1949[3] and independently by Renato Dulbecco also in 1949.[4][5][6]
Photolyases bind complementaryDNA strands and break certain types ofpyrimidine dimers that arise when a pair ofthymine orcytosine bases on the same strand of DNA becomecovalently linked. The bond length of this dimerization is shorter than the bond length of normal B-DNA structure which produces an incorrect template for replication and transcription.[7] The more common covalent linkage involves the formation of acyclobutane bridge. Photolyases have a high affinity for these lesions and reversibly bind and convert them back to the original bases. The photolyase-catalyzed DNA repair process by which cyclobutane pyrimidine dimers are resolved has been studied by time-resolved crystallography and computational analysis to allow atomic visualization of the process.[8]
Photolyase is aphylogenetically old enzyme which is present and functional in many species, from thebacteria to thefungi toplants[9] and to theanimals.[10] 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 efficientnucleotide excision repair mechanism, although they do retain manycryptochromes.[11] Freezing stress in the annual wheatTriticum aestivum and in its perennial relativeThinopyrum intermedium is accompanied by large increases in expression of DNA photolyases.[12]
Photolyases areflavoproteins and contain two light-harvestingcofactors. Many photolyases have anN-terminal domain that binds a second cofactor. All photolyases contain the two-electron-reducedFADH−; they are divided into two main classes based on the second cofactor, which may be either thepterin methenyltetrahydrofolate (MTHF) infolate photolyases or thedeazaflavin 8-hydroxy-7,8-didemethyl-5-deazariboflavin (8-HDF) indeazaflavin photolyases. Although only FAD is required for catalytic activity, the second cofactor significantly accelerates reaction rate in low-light conditions. The enzyme acts byelectron transfer in which the reduced flavin FADH− is activated by light energy and acts as an electron donor to break the pyrimidine dimer.[13]
On the basis of sequence similarities DNA photolyases can be grouped into a few classes:[14][15]
Class 1 CPD photolyases are enzymes that process cyclobutane pyrimidine dimer (CPD) lesions from Gram-negative and Gram-positive bacteria, as well as the halophilicarchaeaHalobacterium halobium.[16]
Class 2 CPD photolyases also process CPD lesions. They are found in plants like the thale cressArabidopsis thaliana and therice.
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 ofcircadian 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 includeVibrio cholerae, X1Cry fromXenopus laevis, and AtCry3 fromArabidopsis thaliana.[10] DASH was initially named afterDrosophila,Arabidopsis,Synechocystis, andHuman, 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.[14]
Eukaryotic(6-4)DNA photolyases form a group with animal cryptochromes that control circadian rhythms. They are found in diverse species includingDrosophila and humans. The cryptochromes have their own detailed grouping.[15]
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.[15] The cryptochromes form apolyphyletic group including photolyases that have lost their DNA repair activity and instead control circadian rhythms.[14][15]
Thesystematic name of this enzyme class isdeoxyribocyclobutadipyrimidine pyrimidine-lyase. Other names in common use includephotoreactivating 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), anddeoxyribonucleate pyrimidine dimer lyase (photosensitive). This enzyme belongs to the family oflyases, specifically in the "catch-all" class of carbon-carbon lyases.
^Yamamoto J, Shimizu K, Kanda T, Hosokawa Y, Iwai S, Plaza P, Müller P (October 2017). "Loss of Fourth Electron-Transferring Tryptophan in Animal (6-4) Photolyase Impairs DNA Repair Activity in Bacterial Cells".Biochemistry.56 (40):5356–64.doi:10.1021/acs.biochem.7b00366.PMID28880077.
^Friedberg EC (September 2015). "A history of the DNA repair and mutagenesis field: I. The discovery of enzymatic photoreactivation".DNA Repair (Amst).33:35–42.doi:10.1016/j.dnarep.2015.06.007.PMID26151545.
^Maestre-Reyna M, Wang PH, Nango E, Hosokawa Y, Saft M, Furrer A, Yang CH, Gusti Ngurah Putu EP, Wu WJ, Emmerich HJ, Caramello N, Franz-Badur S, Yang C, Engilberge S, Wranik M, Glover HL, Weinert T, Wu HY, Lee CC, Huang WC, Huang KF, Chang YK, Liao JH, Weng JH, Gad W, Chang CW, Pang AH, Yang KC, Lin WT, Chang YC, Gashi D, Beale E, Ozerov D, Nass K, Knopp G, Johnson PJ, Cirelli C, Milne C, Bacellar C, Sugahara M, Owada S, Joti Y, Yamashita A, Tanaka R, Tanaka T, Luo F, Tono K, Zarzycka W, Müller P, Alahmad MA, Bezold F, Fuchs V, Gnau P, Kiontke S, Korf L, Reithofer V, Rosner CJ, Seiler EM, Watad M, Werel L, Spadaccini R, Yamamoto J, Iwata S, Zhong D, Standfuss J, Royant A, Bessho Y, Essen LO, Tsai MD (December 2023). "Visualizing the DNA repair process by a photolyase at atomic resolution".Science.382 (6674): eadd7795.Bibcode:2023Sci...382d7795M.doi:10.1126/science.add7795.PMID38033054.
^Jaikumar NS, Dorn KM, Baas D, Wilke B, Kapp C, Snapp SS (December 2020). "Nucleic acid damage and DNA repair are affected by freezing stress in annual wheat (Triticum aestivum) and by plant age and freezing in its perennial relative (Thinopyrum intermedium)".Am J Bot.107 (12):1693–1709.doi:10.1002/ajb2.1584.PMID33340368.
^Sancar A (June 2003). "Structure and function of DNA photolyase and cryptochrome blue-light photoreceptors".Chemical Reviews.103 (6):2203–37.doi:10.1021/cr0204348.PMID12797829.
Eker AP, Fichtinger-Schepman AM (1975). "Studies on a DNA photoreactivating enzyme from Streptomyces griseus II. Purification of the enzyme".Biochim. Biophys. Acta.378 (1):54–63.doi:10.1016/0005-2787(75)90136-7.PMID804322.
Setlow JK, Bollum FJ (1968). "The minimum size of the substrate for yeast photoreactivating enzyme".Biochim. Biophys. Acta.157 (2):233–7.doi:10.1016/0005-2787(68)90077-4.PMID5649902.
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