Model Studies of DNA Photorepair: Enthalpy of Cleavage of a Pyrimidine Dimer Measured by Photothermal Beam Deflection Calorimetry

Scannell, Michael P.; Yeh, Syun Ru; Falvey, Daniel E.

doi:10.1111/j.1751-1097.1996.tb01832.x

Cited by 10 publications

(8 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The experimental Δ r H of opening the neutral dimer of 1,3-dimethylthymine in CH 3 CN is −19 kcal/mol. 46 Our computational result is consistent with the experimental result.…”

Section: Discussionsupporting

confidence: 89%

Exploring Cycloreversion Reaction of Cyclobutane Pyrimidine Dimers Quantum Mechanically

Huang

Chen

et al. 2019

J. Phys. Chem. A

View full text Add to dashboard Cite

The cyclobutane pyrimidine dimer (CPD) is a major photoproduct of deoxyribonucleic acid (DNA) that is damaged by ultraviolet light. This DNA lesion can be repaired by DNA photolyase with the aid of UV light and two cofactors. To understand the repair mechanism of CPD and whether protonation of CPD participates in the DNA repair process, the cycloreversion reactions of four CPD models and proton transfers between the adjacent residue Glu283 and CPD models were explored through the quantum mechanical method. Two-dimensional maps of potential energy surface in a vacuum and in implicit water solution were calculated at the ωB97XD/ 6-311++G(2df,2pd) level. One-dimensional potential energy profiles were computed for proton transfer reactions. Among the models that have been considered, both in a vacuum and in water solution, the results indicate that the most likely repair mechanism involves CPD •2− radical anion splitting in a stepwise manner. C5−C5′ splits first, and C6−C6′ splits later. The computed free energies of activation of the two splitting steps are 0.9 and 3.1 kcal/mol, respectively. The adjacent Glu283 may stabilize the CPD •2− radical anion through hydrogen bond and increase the quantum yield; however, protonating the CPD radical anion by Glu283 cannot accelerate the rate of ring opening.

show abstract

“…The experimental Δ r H of opening the neutral dimer of 1,3-dimethylthymine in CH 3 CN is −19 kcal/mol. 46 Our computational result is consistent with the experimental result.…”

Section: Discussionsupporting

confidence: 89%

Exploring Cycloreversion Reaction of Cyclobutane Pyrimidine Dimers Quantum Mechanically

Huang

Chen

et al. 2019

J. Phys. Chem. A

View full text Add to dashboard Cite

show abstract

“…The thermodynamic cycle illustrated in Figure can be used to calculate the enthalpy change of the splitting reaction. Using a photothermal technique, we have previously estimated the neutral-to-neutral enthalpy of dimer splitting (Δ H neutral ) at −19 kcal/mol for DMTD . (Diogo et al .…”

Section: Resultsmentioning

confidence: 99%

“…The reduction potentials of the dimer DMTD (= DMT〈〉DMT in the figure) and monomer DMT are taken from this work (Table ). The enthalpy for neutral splitting, Δ H neutral , is taken from ref . …”

Section: Resultsmentioning

confidence: 99%

“…Using a photothermal technique, we have previously estimated the neutral-to-neutral enthalpy of dimer splitting (∆H neutral ) at -19 kcal/mol for DMTD. 67 (Diogo et al 68 obtained a value of -26 kcal/mol using a derivative of DMTD where the two bases were linked at their respective N3 positions with a trimethylene bridge.) The reduction potentials of the DMT and DMTD determined here provide the energy difference between the neutral forms and the anion radicals.…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Model Studies of DNA Photorepair: Reduction Potentials of Thymine and Cytosine Cyclobutane Dimers Measured by Fluorescence Quenching

et al. 1997

Self Cite

View full text Add to dashboard Cite

The interactions of various pyrimidines (1,3-dimethylthymine, DMT, 1,3-bis(N 4 ,N 4 -dimethylcytosin-1yl)propane, DMC) and their corresponding cis-syn cyclobutane dimers (DMTD and DMCD) with a series of excitedstate electron donors were examined with the goal of understanding the energetics and mechanism of UV repair by DNA photolyase. For each substrate there is a good correlation between the excited state oxidation potential (E ox *) and the quenching rate constant (k q ). The value for k q increases as E ox * becomes more negative, asymptotically approaching a value that is at or below the solvent diffusion limit. These data all showed good fits to the Rehm-Weller equation. Reduction potentials for each of the substrates could be extracted from this analysis: -2.20 V (vs SCE) for DMTD; -2.14 V for DMT; -2.17 V for DMCD; and -2.16 for DMC. These values show that the initial electron transfer step in the photolyase mechanism is exergonic by ca. 10-15 kcal/mol. Thus these data support the reductive electron transfer mechanism for DNA photolyases proposed by Jorns et al.

show abstract

“…The CPD photolyase mechanism has been studied extensively. A variety of flash spectroscopic [24][25][26][27][28][29] and model studies [30][31][32][33][34][35][36][37][38] indicate that the primary photochemical step is one-electron transfer from the excited chromophore (a reduced flavin, FADH -) to the pyr<>pyr group. 24,[26][27][28][29]34,39,40 The pyr<>pyr -• thus formed splits rapidly and spontaneously in solution.…”

Section: Introductionmentioning

confidence: 99%

Model Studies of the (6−4) Photoproduct Photolyase Enzyme: Laser Flash Photolysis Experiments Confirm Radical Ion Intermediates in the Sensitized Repair of Thymine Oxetane Adducts

2000

Self Cite

View full text Add to dashboard Cite

The DNA (6-4) photoproduct photolyases are proteins that bind to UV-damaged DNA, specifically to sites that contain a (6-4) pyrimidine-pyrimidone lesion. Upon absorption of UV-A and visible light they catalyze the reversal of these lesions back to normal bases. It has been proposed that the photorepair occurs via an oxetane intermediate, which is formed from a ring-closing isomerization of the (6-4) photoproduct. Four model compounds for the oxetane intermediate have been prepared through photocycloaddition of carbonyl compounds (benzophenone, benzaldehyde, tolualdehyde, and anisaldehyde) with the 5,6 CdC of 1,3dimethylthymine. The behavior of these compounds under sensitized photolysis conditions has been examined. On the basis of laser flash photolysis, fluorescence quenching, and product analysis experiments, it is demonstrated that these oxetane intermediates undergo a cycloreversion reaction upon photosensitized reductive electron-transfer reactions. The cycloreversion process yields the anion radicals of the carbonyl compounds. A lower limit on the rate constant of this anion radical splitting reaction is estimated to be >5 × 10 7 s -1 . These results support the proposed mechanism for DNA (6-4) photoproduct photolyase.

show abstract

Model Studies of DNA Photorepair: Enthalpy of Cleavage of a Pyrimidine Dimer Measured by Photothermal Beam Deflection Calorimetry

Cited by 10 publications

References 24 publications

Exploring Cycloreversion Reaction of Cyclobutane Pyrimidine Dimers Quantum Mechanically

Exploring Cycloreversion Reaction of Cyclobutane Pyrimidine Dimers Quantum Mechanically

Model Studies of DNA Photorepair: Reduction Potentials of Thymine and Cytosine Cyclobutane Dimers Measured by Fluorescence Quenching

Model Studies of the (6−4) Photoproduct Photolyase Enzyme: Laser Flash Photolysis Experiments Confirm Radical Ion Intermediates in the Sensitized Repair of Thymine Oxetane Adducts

Contact Info

Product

Resources

About