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Femtosecond stimulated Raman spectroscopy of the cyclobutane thymine dimer repair mechanism: a computational study.

Ando H, Fingerhut BP, Dorfman KE, Biggs JD, Mukamel S - J. Am. Chem. Soc. (2014)

Bottom Line: Cyclobutane thymine dimer, one of the major lesions in DNA formed by exposure to UV sunlight, is repaired in a photoreactivation process, which is essential to maintain life.The molecular mechanism of the central step, i.e., intradimer C-C bond splitting, still remains an open question.The sequential mechanism shows only absorptive features in the simulated FSRS signals, whereas the fast concerted mechanism shows characteristic dispersive line shapes.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry, 1102 Natural Sciences II, University of California , Irvine, California 92697-2025, United States.

ABSTRACT
Cyclobutane thymine dimer, one of the major lesions in DNA formed by exposure to UV sunlight, is repaired in a photoreactivation process, which is essential to maintain life. The molecular mechanism of the central step, i.e., intradimer C-C bond splitting, still remains an open question. In a simulation study, we demonstrate how the time evolution of characteristic marker bands (C═O and C═C/C-C stretch vibrations) of cyclobutane thymine dimer and thymine dinucleotide radical anion, thymidylyl(3'→5')thymidine, can be directly probed with femtosecond stimulated Raman spectroscopy (FSRS). We construct a DFT(M05-2X) potential energy surface with two minor barriers for the intradimer C₅-C₅' splitting and a main barrier for the C₆-C₆' splitting, and identify the appearance of two C₅═C₆ stretch vibrations due to the C₆-C₆' splitting as a spectroscopic signature of the underlying bond splitting mechanism. The sequential mechanism shows only absorptive features in the simulated FSRS signals, whereas the fast concerted mechanism shows characteristic dispersive line shapes.

No MeSH data available.


Related in: MedlinePlus

Kinetic evolution of the closed, INT1•–, INT2•–, and open form (solid blue, purple,yellow, and green) populations of (a) the TpT•– and (b) whole photoreactivation system. In intradimer bond splittingsof the TpT•–, the initially populated stateis the closed form. In entire photoreactivation, the initially populatedstate is FADH–*, and the concentrations of FADH–* and neutral open form are also shown (broken blueand purple). See Supporting Information for the detailed calculation method.
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fig7: Kinetic evolution of the closed, INT1•–, INT2•–, and open form (solid blue, purple,yellow, and green) populations of (a) the TpT•– and (b) whole photoreactivation system. In intradimer bond splittingsof the TpT•–, the initially populated stateis the closed form. In entire photoreactivation, the initially populatedstate is FADH–*, and the concentrations of FADH–* and neutral open form are also shown (broken blueand purple). See Supporting Information for the detailed calculation method.

Mentions: The calculated ratefor the C6—C6′ splittingis slow (14.1 ps), compared to the rates of the two preceding processes(95.4 fs and 1.39 ps), and the kinetics is also closely related withthe sequential mechanism proposed from experiments.6 This is clear from the time-dependent populations of theclosed, INT1•–, INT2•–, and open forms, shown in Figure 7a. Thepopulation of INT2•– reaches its maximumaround 4 ps, while the others have much smaller values. The calculatedsplitting rates are on the same order as the experimental ones byLiu et al.,6 and at least 10 times fasterthan the corresponding back reaction rates (TableS3).


Femtosecond stimulated Raman spectroscopy of the cyclobutane thymine dimer repair mechanism: a computational study.

Ando H, Fingerhut BP, Dorfman KE, Biggs JD, Mukamel S - J. Am. Chem. Soc. (2014)

Kinetic evolution of the closed, INT1•–, INT2•–, and open form (solid blue, purple,yellow, and green) populations of (a) the TpT•– and (b) whole photoreactivation system. In intradimer bond splittingsof the TpT•–, the initially populated stateis the closed form. In entire photoreactivation, the initially populatedstate is FADH–*, and the concentrations of FADH–* and neutral open form are also shown (broken blueand purple). See Supporting Information for the detailed calculation method.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4210081&req=5

fig7: Kinetic evolution of the closed, INT1•–, INT2•–, and open form (solid blue, purple,yellow, and green) populations of (a) the TpT•– and (b) whole photoreactivation system. In intradimer bond splittingsof the TpT•–, the initially populated stateis the closed form. In entire photoreactivation, the initially populatedstate is FADH–*, and the concentrations of FADH–* and neutral open form are also shown (broken blueand purple). See Supporting Information for the detailed calculation method.
Mentions: The calculated ratefor the C6—C6′ splittingis slow (14.1 ps), compared to the rates of the two preceding processes(95.4 fs and 1.39 ps), and the kinetics is also closely related withthe sequential mechanism proposed from experiments.6 This is clear from the time-dependent populations of theclosed, INT1•–, INT2•–, and open forms, shown in Figure 7a. Thepopulation of INT2•– reaches its maximumaround 4 ps, while the others have much smaller values. The calculatedsplitting rates are on the same order as the experimental ones byLiu et al.,6 and at least 10 times fasterthan the corresponding back reaction rates (TableS3).

Bottom Line: Cyclobutane thymine dimer, one of the major lesions in DNA formed by exposure to UV sunlight, is repaired in a photoreactivation process, which is essential to maintain life.The molecular mechanism of the central step, i.e., intradimer C-C bond splitting, still remains an open question.The sequential mechanism shows only absorptive features in the simulated FSRS signals, whereas the fast concerted mechanism shows characteristic dispersive line shapes.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry, 1102 Natural Sciences II, University of California , Irvine, California 92697-2025, United States.

ABSTRACT
Cyclobutane thymine dimer, one of the major lesions in DNA formed by exposure to UV sunlight, is repaired in a photoreactivation process, which is essential to maintain life. The molecular mechanism of the central step, i.e., intradimer C-C bond splitting, still remains an open question. In a simulation study, we demonstrate how the time evolution of characteristic marker bands (C═O and C═C/C-C stretch vibrations) of cyclobutane thymine dimer and thymine dinucleotide radical anion, thymidylyl(3'→5')thymidine, can be directly probed with femtosecond stimulated Raman spectroscopy (FSRS). We construct a DFT(M05-2X) potential energy surface with two minor barriers for the intradimer C₅-C₅' splitting and a main barrier for the C₆-C₆' splitting, and identify the appearance of two C₅═C₆ stretch vibrations due to the C₆-C₆' splitting as a spectroscopic signature of the underlying bond splitting mechanism. The sequential mechanism shows only absorptive features in the simulated FSRS signals, whereas the fast concerted mechanism shows characteristic dispersive line shapes.

No MeSH data available.


Related in: MedlinePlus