Photolyase

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Cryptochrome/photolyase, C-terminal, FAD binding
Photolyase 1qnf.png
A deazaflavin photolyase from Anacystis nidulans , illustrating the two light-harvesting cofactors: FADH (yellow) and 8-HDF (cyan).
Identifiers
SymbolFAD_binding_7
Pfam PF03441
InterPro IPR005101
PROSITE PDOC00331
SCOP2 1qnf / SCOPe / SUPFAM
Available protein structures:
Pfam   structures / ECOD  
PDB RCSB PDB; PDBe; PDBj
PDBsum structure summary
PDB 1u3c A:214-492 1u3d A:214-492 1iqu A:176-418

1iqr A:176-418 1dnp B:202-469 1tez D:207-472 1owm A:207-472 1qnf :207-472 1owp A:207-472 1owo A:207-472 1owl A:207-472 1own A:207-472

Contents

1np7 B:213-453
deoxyribodipyrimidine photo-lyase (CPD)
Direct DNA damage.png
A UV radiation induced thymine-thymine cyclobutane dimer (right) is the type of DNA damage which is repaired by DNA photolyase. Note: The above diagram is incorrectly labelled as thymine as the structures lack 5-methyl groups.
Identifiers
EC no. 4.1.99.3
CAS no. 37290-70-3
Databases
IntEnz IntEnz view
BRENDA BRENDA entry
ExPASy NiceZyme view
KEGG KEGG entry
MetaCyc metabolic pathway
PRIAM profile
PDB structures RCSB PDB PDBe PDBsum
Gene Ontology AmiGO / QuickGO
Search
PMC articles
PubMed articles
NCBI proteins

Photolyases (EC 4.1.99.3) are DNA repair enzymes that repair damage caused by exposure to ultraviolet light. These enzymes require visible 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 first DNA 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]

Function

Photolyases bind complementary DNA strands and break certain types of pyrimidine dimers that arise when a pair of thymine or cytosine bases on the same strand of DNA become covalently 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 a cyclobutane 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]

Evolution

Photolyase is a phylogenetically old enzyme which is present and functional in many species, from the bacteria to the fungi to plants [9] and to the animals. [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 efficient nucleotide excision repair mechanism, although they do retain many cryptochromes. [11] 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. [12]

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. [13]

On the basis of sequence similarities DNA photolyases can be grouped into a few classes: [14] [15]

Cryptochrome/photolyase family (2015) [14]

FeS-BCP

CPD-2

CPD-1

CPD-3gre

Plant Cry

P. tricornutum CryP]

Cry-DASH

Eukaryotic 6-4; Animal Cry

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 a polyphyletic group including photolyases that have lost their DNA repair activity and instead control circadian rhythms. [14] [15]

Application

Adding photolyase from a blue-green algae Anacystis nidulans, to HeLa cells partially reduced DNA damage from UVB exposure. [17]

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.

Related Research Articles

Cyclobutane is a cycloalkane and organic compound with the formula (CH2)4. Cyclobutane is a colourless gas and is commercially available as a liquefied gas. Derivatives of cyclobutane are called cyclobutanes. Cyclobutane itself is of no commercial or biological significance, but more complex derivatives are important in biology and biotechnology.

<span class="mw-page-title-main">Cryptochrome</span> Class of photoreceptors in plants and animals

Cryptochromes are a class of flavoproteins found in plants and animals that are sensitive to blue light. They are involved in the circadian rhythms and the sensing of magnetic fields in a number of species. The name cryptochrome was proposed as a portmanteau combining the chromatic nature of the photoreceptor, and the cryptogamic organisms on which many blue-light studies were carried out.

<span class="mw-page-title-main">Aziz Sancar</span> Turkish biochemist and molecular biologist

Aziz Sancar is a Turkish molecular biologist specializing in DNA repair, cell cycle checkpoints, and circadian clock. In 2015, he was awarded the Nobel Prize in Chemistry along with Tomas Lindahl and Paul L. Modrich for their mechanistic studies of DNA repair. He has made contributions on photolyase and nucleotide excision repair in bacteria that have changed his field.

<span class="mw-page-title-main">Pyrimidine dimer</span> Type of damage to DNA

Pyrimidine dimers represent molecular lesions originating from thymine or cytosine bases within DNA, resulting from photochemical reactions. These lesions, commonly linked to direct DNA damage, are induced by ultraviolet light (UV), particularly UVC, result in the formation of covalent bonds between adjacent nitrogenous bases along the nucleotide chain near their carbon–carbon double bonds, the photo-coupled dimers are fluorescent. Such dimerization, which can also occur in double-stranded RNA (dsRNA) involving uracil or cytosine, leads to the creation of cyclobutane pyrimidine dimers (CPDs) and 6–4 photoproducts. These pre-mutagenic lesions modify the DNA helix structure, resulting in abnormal non-canonical base pairing and, consequently, adjacent thymines or cytosines in DNA will form a cyclobutane ring when joined together and cause a distortion in the DNA. This distortion prevents DNA replication and transcription mechanisms beyond the dimerization site.

<span class="mw-page-title-main">Histidine ammonia-lyase</span>

Histidine ammonia-lyase is an enzyme that in humans is encoded by the HAL gene. It converts histidine into ammonia and urocanic acid. Its systematic name is L-histidine ammonia-lyase (urocanate-forming).

Postreplication repair is the repair of damage to the DNA that takes place after replication.

<span class="mw-page-title-main">POLI</span> Protein-coding gene in the species Homo sapiens

DNA polymerase iota is an enzyme that in humans is encoded by the POLI gene. It is found in higher eukaryotes, and is believed to have arisen from a gene duplication from Pol η. Pol ι, is a Y family polymerase that is involved in translesion synthesis. It can bypass 6-4 pyrimidine adducts and abasic sites and has a high frequency of wrong base incorporation. Like many other Y family polymerases Pol ι, has low processivity, a large DNA binding pocket and doesn't undergo conformational changes when DNA binds. These attributes are what allow Pol ι to carry out its task as a translesion polymerase. Pol ι only uses Hoogsteen base pairing, during DNA synthesis, it will add adenine opposite to thymine in the syn conformation and can add both cytosine and thymine in the anti conformation across guanine, which it flips to the syn conformation.

<span class="mw-page-title-main">1-Aminocyclopropane-1-carboxylate synthase</span> Class of enzymes

The enzyme aminocyclopropane-1-carboxylic acid synthase catalyzes the synthesis of 1-Aminocyclopropane-1-carboxylic acid (ACC), a precursor for ethylene, from S-Adenosyl methionine, an intermediate in the Yang cycle and activated methyl cycle and a useful molecule for methyl transfer:

<span class="mw-page-title-main">Cystathionine beta-lyase</span> Enzyme

Cystathionine beta-lyase, also commonly referred to as CBL or β-cystathionase, is an enzyme that primarily catalyzes the following α,β-elimination reaction

<span class="mw-page-title-main">Aminodeoxychorismate synthase</span>

In enzymology, an aminodeoxychorismate synthase is an enzyme that catalyzes the chemical reaction

<span class="mw-page-title-main">ERCC8 (gene)</span> Protein-coding gene in humans

DNA excision repair protein ERCC-8 is a protein that in humans is encoded by the ERCC8 gene.

<span class="mw-page-title-main">GTF2H1</span> Protein-coding gene in the species Homo sapiens

General transcription factor IIH subunit 1 is a protein that in humans is encoded by the GTF2H1 gene.

Spore photoproduct lyase is a radical SAM enzyme that repairs DNA cross linking of thymine bases caused by UV-radiation. There are several types of thymine cross linking, but SPL specifically targets 5-thyminyl-5,6-dihydrothymine, which is also called spore photoproduct (SP). Spore photoproduct is the predominant type of thymine crosslinking in germinating endospores, which is why SPL is unique to organisms that produce endospores, such as Bacillus subtilis. Other types of thymine crosslinking, such as cyclobutane pyrimidine dimers (CPD) and pyrimidine (6-4) pyrimidone photoproducts (6-4PPs), are less commonly formed in endospores. These differences in DNA crosslinking are a function of differing DNA structure. Spore genomic DNA features many DNA binding proteins called small acid soluble proteins, which changes the DNA from the traditional B-form conformation to an A-form conformation. This difference in conformation is believed to be the reason why dormant spores predominantly accumulate SP in response to UV-radiation, rather than other forms of cross linking. Spores cannot repair cross-linking while dormant, instead the SPs are repaired during germination to allow the vegetative cell to function normally. When not repaired, spore photoproduct and other types of crosslinking can cause mutations by blocking transcription and replication past the point of the crosslinking. The repair mechanism utilizing spore photoproduct lyase is one of the reasons for the resilience of certain bacterial spores.

Somatic recombination, as opposed to the genetic recombination that occurs in meiosis, is an alteration of the DNA of a somatic cell that is inherited by its daughter cells. The term is usually reserved for large-scale alterations of DNA such as chromosomal translocations and deletions and not applied to point mutations. Somatic recombination occurs physiologically in the assembly of the B cell receptor and T-cell receptor genes, as well as in the class switching of immunoglobulins. Somatic recombination is also important in the process of carcinogenesis.

DNA photolyase, N-terminal is an evolutionary conserved protein domain. This domain binds a light harvesting chromophore that enhanced the spectrum of photolyase or cryptochrome light absorption, i.e. an antenna. It adopts the Rossmann fold.

<span class="mw-page-title-main">FPG IleRS zinc finger</span>

The FPG IleRS zinc finger domain represents a zinc finger domain found at the C-terminal in both DNA glycosylase/AP lyase enzymes and in isoleucyl tRNA synthetase. In these two types of enzymes, the C-terminal domain forms a zinc finger.

<span class="mw-page-title-main">H2TH domain</span>

In molecular biology, the H2TH domain is a DNA-binding domain found in DNA glycosylase/AP lyase enzymes, which are involved in base excision repair of DNA damaged by oxidation or by mutagenic agents. Most damage to bases in DNA is repaired by the base excision repair pathway. These enzymes are primarily from bacteria, and have both DNA glycosylase activity EC 3.2.2.- and AP lyase activity EC 4.2.99.18. Examples include formamidopyrimidine-DNA glycosylases and endonuclease VIII (Nei).

Radical SAM enzymes belong to a superfamily of enzymes that use an iron-sulfur cluster (4Fe-4S) to reductively cleave S-adenosyl-L-methionine (SAM) to generate a radical, usually a 5′-deoxyadenosyl radical (5'-dAdo), as a critical intermediate. These enzymes utilize this radical intermediate to perform diverse transformations, often to functionalize unactivated C-H bonds. Radical SAM enzymes are involved in cofactor biosynthesis, enzyme activation, peptide modification, post-transcriptional and post-translational modifications, metalloprotein cluster formation, tRNA modification, lipid metabolism, biosynthesis of antibiotics and natural products etc. The vast majority of known radical SAM enzymes belong to the radical SAM superfamily, and have a cysteine-rich motif that matches or resembles CxxxCxxC. Radical SAM enzymes comprise the largest superfamily of metal-containing enzymes.

(6-4)DNA photolyase is an enzyme with systematic name (6-4) photoproduct pyrimidine-lyase. This enzyme catalyses the following chemical reaction

Mutational signatures are characteristic combinations of mutation types arising from specific mutagenesis processes such as DNA replication infidelity, exogenous and endogenous genotoxin exposures, defective DNA repair pathways, and DNA enzymatic editing.

References

  1. 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. PMID   28880077.
  2. Thiagarajan V, Byrdin M, Eker AP, Müller P, Brettel K (June 2011). "Kinetics of cyclobutane thymine dimer splitting by DNA photolyase directly monitored in the UV". Proc Natl Acad Sci U S A. 108 (23): 9402–7. Bibcode:2011PNAS..108.9402T. doi: 10.1073/pnas.1101026108 . PMC   3111307 . PMID   21606324.
  3. Kelner A (February 1949). "Effect of Visible Light on the Recovery of Streptomyces Griseus Conidia from Ultra-violet Irradiation Injury". Proc Natl Acad Sci U S A. 35 (2): 73–9. Bibcode:1949PNAS...35...73K. doi: 10.1073/pnas.35.2.73 . PMC   1062964 . PMID   16588862.
  4. Dulbecco R (June 1949). "Reactivation of ultra-violet-inactivated bacteriophage by visible light". Nature. 163 (4155): 949–950. Bibcode:1949Natur.163..949D. doi:10.1038/163949b0. PMID   18229246.
  5. Dulbecco R (March 1950). "Experiments on photoreactivation of bacteriophages inactivated with ultraviolet radiation". J Bacteriol. 59 (3): 329–47. doi:10.1128/jb.59.3.329-347.1950. PMC   385765 . PMID   15436402.
  6. 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. PMID   26151545.
  7. Garrett RH, Grisham CM (2010). Biochemistry. Brooks/Cole, Cengage Learning. ISBN   978-0-495-10935-8. OCLC   984382855.
  8. 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. PMID   38033054.
  9. eranishi M, Nakamura K, Morioka H, Yamamoto K, Hidema J (2008). "The native cyclobutane pyrimidine dimer photolyase of rice is phosphorylated". Plant Physiology. 146 (4): 1941–51. doi:10.1104/pp.107.110189. PMC   2287361 . PMID   18235036.
  10. 1 2 Selby CP, Sancar A (November 2006). "A cryptochrome/photolyase class of enzymes with single-stranded DNA-specific photolyase activity". Proc Natl Acad Sci U S A. 103 (47): 17696–700. Bibcode:2006PNAS..10317696S. doi: 10.1073/pnas.0607993103 . PMC   1621107 . PMID   17062752.
  11. Lucas-Lledó JI, Lynch M (May 2009). "Evolution of mutation rates: phylogenomic analysis of the photolyase/cryptochrome family". Molecular Biology and Evolution. 26 (5): 1143–53. doi:10.1093/molbev/msp029. PMC   2668831 . PMID   19228922.
  12. 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. PMID   33340368.
  13. 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. PMID   12797829.
  14. 1 2 3 4 Scheerer P, Zhang F, Kalms J, von Stetten D, Krauß N, Oberpichler I, Lamparter T (May 2015). "The class III cyclobutane pyrimidine dimer photolyase structure reveals a new antenna chromophore binding site and alternative photoreduction pathways". The Journal of Biological Chemistry. 290 (18): 11504–14. doi: 10.1074/jbc.M115.637868 . PMC   4416854 . PMID   25784552.
  15. 1 2 3 4 Rivera AS, Ozturk N, Fahey B, Plachetzki DC, Degnan BM, Sancar A, Oakley TH (April 2012). "Blue-light-receptive cryptochrome is expressed in a sponge eye lacking neurons and opsin". The Journal of Experimental Biology. 215 (Pt 8): 1278–86. doi:10.1242/jeb.067140. PMC   3309880 . PMID   22442365.
  16. McCready S, Marcello L (June 2003). "Repair of UV damage in Halobacterium salinarum". Biochem Soc Trans. 31 (Pt 3): 694–8. doi:10.1042/bst0310694. PMID   12773185.
  17. Kulms D, Pöppelmann B, Yarosh D, Luger TA, Krutmann J, Schwarz T (July 1999). "Nuclear and cell membrane effects contribute independently to the induction of apoptosis in human cells exposed to UVB radiation". Proc Natl Acad Sci U S A. 96 (14): 7974–9. Bibcode:1999PNAS...96.7974K. doi: 10.1073/pnas.96.14.7974 . PMC   22172 . PMID   10393932.

Further reading