A new photoreactivating enzyme that specifically repairs ultraviolet light-induced (6-4)photoproducts

Todo, Tomoki; Takemori, Hiroshi; Ryo, Haruko; Ihara, Masataka; Matsunaga, Tsukasa; Nikaido, Osamu; Sato, Kazuo; Nomura, Taisei

doi:10.1038/361371a0

Cited by 284 publications

(202 citation statements)

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“…It should also be noted that the DNA repair capacity of Drosophila cells is somewhat different from that of human cells. The most striking difference is that Drosophila cells have a 6 -4-photolyase, which specifically repairs (6 -4)PP in a light-dependent manner, but human cells lack this enzyme (45). The (6 -4)PP lesions are removed rapidly by nucleotide excision repair.…”

Section: Discussionmentioning

confidence: 99%

Mutagenic and Nonmutagenic Bypass of DNA Lesions byDrosophila DNA Polymerases dpolη and dpolι

Ishikawa

Uematsu

Mizukoshi

et al. 2001

Journal of Biological Chemistry

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cDNA sequences were identified and isolated that encode Drosophila homologues of human Rad30A and Rad30B called drad30A and drad30B. Here we show that the C-terminal-truncated forms of the drad30A and drad30B gene products, designated dpol⌬C and dpol⌬C, respectively, exhibit DNA polymerase activity. dpol⌬C and dpol⌬C efficiently bypass a cis-syn-cyclobutane thymine-thymine (TT) dimer in a mostly error-free manner. dpol⌬C shows limited ability to bypass a 6 -4-photoproduct ((6 -4)PP) at thymine-thymine (TT-(6 -4)PP) or at thymine-cytosine (TC-(6 -4)PP) in an error-prone manner. dpol⌬C scarcely bypasses these lesions. Thus, the fidelity of translesion synthesis depends on the identity of the lesion and on the polymerase. The human XPV gene product, hpol, bypasses cis-syn-cyclobutane thymine-thymine dimer efficiently in a mostly error-free manner but does not bypass TT-(6 -4)PP, whereas Escherichia coli DNA polymerase V (UmuD 2 C complex) bypasses both lesions, especially TT-(6 -4)PP, in an error-prone manner (Tang, M., Pham, P., Shen, X., Taylor, J. S., O'Donnell, M., Woodgate, R., and Goodman, M. F. (2000) Nature 404, 1014 -1018). Both dpol⌬C and DNA polymerase V preferentially incorporate GA opposite TT-(6 -4)PP. The chemical structure of the lesions and the similarity in the nucleotides incorporated suggest that structural information in the altered bases contribute to nucleotide selection during incorporation opposite these lesions by these polymerases.DNA is frequently damaged by environmental and endogenous genotoxic agents. Although various mechanisms exist to ensure that the majority of DNA damage is recognized and repaired and the integrity of the DNA is faithfully restored, some DNA lesions escape repair and persist in the cell. Unrepaired DNA lesions can block the progress of the replication machinery. To help resolve this problem, cells have specialized polymerases that carry out translesion DNA synthesis (TLS) 1 , which is a mechanism that permits nucleotides to be incorporated opposite lesions. After TLS bypasses the DNA damage, replication can continue with the normal replication machinery downstream of the site of the damage.Recently, a new family of DNA polymerases was identified called the UmuC/DinB/Rev1/Rad30 superfamily (1-3). Several of these polymerases participate in TLS (4 -11), and members of this protein family exhibit lower fidelity and processivity than replicative DNA polymerases (10, 12-15). The lower fidelity enables these polymerases to carry out TLS and the lower processivity facilitates dissociation of these enzymes after bypass of a lesion; this is important because it allows the normal replication machinery, with high fidelity and processivity, to preferentially carry out DNA synthesis distal to the lesion. However, TLS is mutagenic when the base inserted opposite the DNA lesion is different than the base normally inserted opposite an undamaged base at that site. The chemical structure of the lesion is an important determinant for mutagenic or nonmutagenic bypass during TLS. Irr...

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Section: Discussionmentioning

confidence: 99%

Mutagenic and Nonmutagenic Bypass of DNA Lesions byDrosophila DNA Polymerases dpolη and dpolι

Ishikawa

Uematsu

Mizukoshi

et al. 2001

Journal of Biological Chemistry

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“…CPD photolyase has 20 -30% sequence homology with (6 -4) photolyases and cryptochromes. The (6 -4) photolyase uses light to repair the (6 -4) photoproduct, which is another UV-induced DNA lesion (4,41). Cryptochromes control the light response in plants and animals (42)(43)(44).…”

Section: Discussionmentioning

confidence: 99%

NMR Study of Repair Mechanism of DNA Photolyase by FAD-induced Paramagnetic Relaxation Enhancement

Ueda

Kato

Ogawa

et al. 2004

Journal of Biological Chemistry

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Cyclobutane pyrimidine dimer (CPD) photolyases, which contain FAD as a cofactor, use light to repair CPDs. We performed structural analyses of the catalytic site of the Thermus thermophilus CPD photolyase-DNA complex, using FAD-induced paramagnetic relaxation enhancement (PRE). The distances between the tryptophan residues and the FAD calculated from the PRE agree well with those observed in the x-ray structure (with an error of <3 Å). Subsequently, a single-stranded DNA containing 13 C-labeled CPD was prepared, and the FAD-induced PRE of the NMR resonances from the CPD lesion in complex with the CPD photolyase was investigated. The distance between the FAD and the CPD calculated from the PRE is 16 ؎ 3 Å. The FAD-induced PRE was also observed in the CPD photolyase-doublestranded DNA complex. Based on these results, a model of the CPD photolyase-DNA complex was constructed, and the roles of Arg-201, Lys-240, Trp-247, and Trp-353 in the CPD-repair reaction are discussed.UV irradiation induces various lesions in DNA (1). The cyclobutane pyrimidine dimer (CPD) 1 is a major DNA lesion induced by UV light (2). CPD formation is closely linked to deleterious effects, including mutation, cell death, and skin cancer. Organisms have a variety of enzymes that recognize and repair DNA lesions. CPD photolyases repair CPDs using visible or near-UV light (3, 4). CPD photolyases induce in vivo photoreactivation, which prevents the deleterious effects of far-UV light (200 -300 nm) by the concurrent or subsequent exposure to near-UV-visible (300 -500 nm) light.CPD photolyases contain FAD as a catalytic cofactor. CPD photolyases repair the CPD by an electron transfer from photoactivated FAD to the CPD. The high quantum yield of the reaction ( ϭ 0.5-1.0) shows that CPD photolyases utilize light energy quite efficiently (5, 6). According to the theory proposed by Marcus (7), the distance and the relative orientation between donors and acceptors determines the efficiency of electron transfer reactions. Therefore, a structural analysis of the catalytic site of the enzyme is important for understanding the mechanism of the high efficiency of the reaction.The crystal structures of the CPD photolyases from Escherichia coli, Anacystis nidulans, and Thermus thermophilus HB8 were recently solved (8 -10). These structures show a similar global fold, and they have an FAD-containing cavity in the C-terminal helical domain. The crystal structure of the T. thermophilus CPD photolyase-thymine complex has also been solved (10). In this structure, the thymine molecule resided in the cavity, suggesting that this cavity forms the CPD-binding site. However, the structure of a CPD photolyase in complex with CPD-containing DNA has not yet been determined.Unpaired electrons induce paramagnetic relaxation enhancement (PRE) in NMR resonances from neighboring atoms in a distance-dependent manner, and the relaxation data are calculated with the Solomon-Bloembergen equation (11). PRE has been used for analyses of denatured proteins (12-14), protein-ligand comp...

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“…Recombinant DNA technology considerably accelerated the pace of characterization of these enzymes (4 -7). However, it was only in 1993 that a photolyase that repairs the (6-4) photoproduct was also discovered (8). Similarly, in 1993, it was found that an Arabidopsis thaliana protein with high sequence homology to photolyase had no repair activity but functioned as a blue-light receptor (cryptochrome) for plant growth and development (9).…”

Section: Historical Perspectivementioning

confidence: 99%

Structure and Function of Photolyase and in Vivo Enzymology: 50th Anniversary

Sancar

2008

Journal of Biological Chemistry

179

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A new photoreactivating enzyme that specifically repairs ultraviolet light-induced (6-4)photoproducts

Cited by 284 publications

References 19 publications

Mutagenic and Nonmutagenic Bypass of DNA Lesions byDrosophila DNA Polymerases dpolη and dpolι

Mutagenic and Nonmutagenic Bypass of DNA Lesions byDrosophila DNA Polymerases dpolη and dpolι

NMR Study of Repair Mechanism of DNA Photolyase by FAD-induced Paramagnetic Relaxation Enhancement

Structure and Function of Photolyase and in Vivo Enzymology: 50th Anniversary

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