Solution-state structure of a DNA dodecamer duplex containing a Cis-Syn thymine cyclobutane dimer, the major UV photoproduct of DNA

McAteer, Kathleen; Jing, Y.; Kao, Jeffrey L.-F.; Taylor, John‐Stephen; Kennedy, Michael A.

doi:10.1006/jmbi.1998.2062

Cited by 123 publications

(169 citation statements)

References 64 publications

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“…In addition to the chemical structure of the CPD base, the B II conformation of the backbone flanking the CPD on the 3Ј-side is the most pronounced characteristic of the CPD-containing dsDNA structure (30). Thus, the CPD photolyase may recognize the B II conformation of the backbone in the first step of DNA recognition.…”

Section: Table II Analyses Of the Interactions Between The Cpd Photolmentioning

confidence: 99%

“…However, as described above, the bases of the CPD exist inside the CPD-containing dsDNA in the free form (30). The difference between the DNA structures in the free and bound forms raises the question of how the CPD photolyase recognizes the CPD in dsDNA.…”

Section: Table II Analyses Of the Interactions Between The Cpd Photolmentioning

confidence: 99%

“…Flipping of CPD from the DNA Duplex in the Complex-The CPD photolyase is reportedly able to recognize and repair a CPD lesion embedded in dsDNA as well as that in ssDNA (24 -30), although McAteer et al (30) reported that a CPD in dsDNA exists within the DNA helix and forms Watson-Crick type hydrogen-bonds with the complementary strand. One possible recognition mode for the buried CPD in dsDNA by the CPD photolyase is that the enzyme unwinds the dsDNA and then recognizes the CPD in dsDNA.…”

Section: Table II Analyses Of the Interactions Between The Cpd Photolmentioning

confidence: 99%

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Investigation of the Cyclobutane Pyrimidine Dimer (CPD) Photolyase DNA Recognition Mechanism by NMR Analyses

Torizawa

Ueda

Kuramitsu

et al. 2004

Journal of Biological Chemistry

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The cyclobutane pyrimidine dimer (CPD) is one of the major forms of DNA damage caused by irradiation with ultraviolet (UV) light. CPD photolyases recognize and repair UV-damaged DNA. The DNA recognition mechanism of the CPD photolyase has remained obscure because of a lack of structural information about DNA-CPD photolyase complexes. In order to elucidate the CPD photolyase DNA binding mode, we performed NMR analyses of the DNA-CPD photolyase complex. Based upon results from 31 P NMR measurements, in combination with site-directed mutagenesis, we have demonstrated the orientation of CPD-containing single-stranded DNA (ssDNA) on the CPD photolyase. In addition, chemical shift perturbation analyses, using stable isotope-labeled DNA, revealed that the CPD is buried in a cavity within CPD photolyase. Finally, NMR analyses of a double-stranded DNA (dsDNA)-CPD photolyase complex indicated that the CPD is flipped out of the dsDNA by the enzyme, to gain access to the active site.Irradiation of DNA with ultraviolet (UV) light produces various damaged bases, leading to cellular transformation and cell death (1-3). One of the major products formed by UV irradiation is the cyclobutane pyrimidine dimer (CPD) 1 (Fig. 1), from the photo [2 ϩ 2] cycloaddition of the 5,6-double bond of two adjacent pyrimidine nucleotides. Organisms have a variety of enzymes playing crucial roles in repair-systems for damaged DNA, including nucleoside excision repair systems and photoreactivation (4). CPD photolyases, which function as members of the DNA repair systems, restore the CPD to normal pyrimidines by photoreactivation. To elucidate the mechanism of DNA repair by CPD photolyase, various biological and spectroscopic experiments have been performed. This enzyme has a flavin adenine dinucleotide (FAD) as an essential cofactor (5).The FAD is excited by light, and then transfers one electron to the CPD bases (6 -8). After the electron transfer, the cyclobutane ring splits and then one electron is transferred back to the FAD (9, 10). In order to understand the mechanism based on structural analyses, the crystal structures of the CPD photolyases from Escherichia coli, Anacystis nidulans, and Thermus thermophilus have been solved without the substrates, i.e. CPD-containing DNAs (11-13). The x-ray studies revealed that the enzymes share a similar global fold, which consists of an ␣/␤ domain and a helical domain. The helical domain is composed of clusters I and II, and a cavity is formed between the clusters, where the FAD is deeply buried. It has been suggested that the cavity is used for the CPD binding, because the asymmetric polarity of the cavity fits well with that of the CPD (11-15). Based upon the crystal structures without the substrates, two research groups have proposed computer models of the DNA-CPD photolyase complex, in which the relative orientations of the DNA chain are different from each other (11-15). However, no crystallographic or NMR structure information on the complexes is presently available.Here, we report NMR analyses of...

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Section: Table II Analyses Of the Interactions Between The Cpd Photolmentioning

confidence: 99%

Section: Table II Analyses Of the Interactions Between The Cpd Photolmentioning

confidence: 99%

Section: Table II Analyses Of the Interactions Between The Cpd Photolmentioning

confidence: 99%

See 1 more Smart Citation

Investigation of the Cyclobutane Pyrimidine Dimer (CPD) Photolyase DNA Recognition Mechanism by NMR Analyses

Torizawa

Ueda

Kuramitsu

et al. 2004

Journal of Biological Chemistry

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“…If under the formation of the cis-syn cyclobutane pyrimidine dimer tautomeric states of its constituent bases has changed, such rare tautomeric states will be stable [82,84]. The rare tautomeric forms of bases are stable because, at cis-syn cyclobutane pyrimidine dimers formation, the DNA strand is bent and the hydrogen bonds between the bases are significantly weakened or are broken [123][124][125][126]. When the hydrogen bond becomes weaker it becomes longer.…”

Section: The Reasons For the Stability Of The Rare Tautomeric Forms Omentioning

confidence: 99%

“…If next to the bases in rare tautomeric forms will be cyclobutane dimers is every reason to remain in his rare tautomeric forms. This is because during the formation of cyclobutane pyrimidine dimer DNA strand is curved, loop occurs, hydrogen bonds are broken [123][124][125][126]. Hydrogen atoms are unable to return to their former states; they are no longer associated with their partners via hydrogen bonds [82].…”

Section: /14mentioning

confidence: 99%

A Polymerase Tautomeric Model for Radiation Induced Bystander Effects: A Model for Untargeted Base Substitution Mutagenesis during Error Prone and SOS Replication of Double Stranded DNA Containing Thymine and Adenine in Rare Tautomeric Forms

Grebneva¹

2017

IJMBOA

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Currently, untargeted mutations are studied in the context of bystander effects. Up to now the nature and mechanisms of formation of untargeted mutations is poorly understood. Untargeted base substitution mutations are base substitution mutations then one or some nucleotides are inserted in DNA molecule on, so called, undamaged sites of DNA. Here the polymerase-tautomeric models of ultraviolet mutagenesis and bystander effects are developed. The mechanisms of untargeted base substitution mutations formation caused by cis-syn cyclobutane thymine dimers and bases pairs of adenine-thymine or thymine-adenine in rare tautomeric forms that are in small neighbor from any cyclobutane dimers are proposed. Five rare tautomeric forms may form for thymine and adenine. These rare tautomeric forms will be stable if corresponding nucleotides are part of cyclobutane pyrimidine dimers or are in small neighbor of the cyclobutane dimers and during DNA synthesis. Structural analysis of bases incorporation shown that adenine in rare tautomeric form A 1

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A Comparative Repair Study of Thymine- and Uracil-Photodimers with Model Compounds and a Photolyase Repair Enzyme

et al. 2000

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Cyclobutane uridine and thymidine dimers with cis-syn-structure are DNA lesions, which are efficiently repaired in many species by DNA photolyases. The essential step of the repair reaction is a light driven electron transfer from a reduced FAD cofactor (FADH ) to the dimer lesion, which splits spontaneously into the monomers. Repair studies with UV-light damaged DNA revealed significant rate differences for the various dimer lesions. In particular the effect of the almost eclipsed positioned methyl groups at the thymidine cyclobutane dimer moiety on the splitting rates is unknown. In order to investigate the cleavage vulnerability of thymine and uracil cyclobutane photodimers outside the protein environment, two model compounds, containing a thymine or a uracil dimer and a covalently connected flavin, were prepared and comparatively investigated. Cleavage investigations under internal competition conditions revealed, in contrast to all previous findings, faster repair of the sterically less encumbered uracil dimer. Stereoelectronic effects are offered as a possible explanation. Ab initio calculations and X-ray crystal structure data reveal a different cyclobutane ring pucker of the uracil dimer, which leads to a better overlap of the pi*-C(4)-O(4)-orbital with the sigma*-C(5)-C(5')-orbital. Enzymatic studies with a DNA photolyase (A. nidulans) and oligonucleotides, which contain either a uridine or a thymidine dimer analogue, showed comparable repair efficiencies for both dimer lesions. Under internal competition conditions significantly faster repair of uridine dimers is observed.

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Solution-state structure of a DNA dodecamer duplex containing a Cis-Syn thymine cyclobutane dimer, the major UV photoproduct of DNA

Cited by 123 publications

References 64 publications

Investigation of the Cyclobutane Pyrimidine Dimer (CPD) Photolyase DNA Recognition Mechanism by NMR Analyses

Investigation of the Cyclobutane Pyrimidine Dimer (CPD) Photolyase DNA Recognition Mechanism by NMR Analyses

A Polymerase Tautomeric Model for Radiation Induced Bystander Effects: A Model for Untargeted Base Substitution Mutagenesis during Error Prone and SOS Replication of Double Stranded DNA Containing Thymine and Adenine in Rare Tautomeric Forms

A Comparative Repair Study of Thymine- and Uracil-Photodimers with Model Compounds and a Photolyase Repair Enzyme

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