Photoenzymic repair of UV-damaged DNA: a chemist's perspective

Heelis, Paul F.; Hartman, Rosemarie F.; Rose, Seth D.

doi:10.1039/cs9952400289

Cited by 166 publications

(170 citation statements)

References 16 publications

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“…Although neither of the two thio analogs of the proposed oxetane or azetidine intermediates were substrates for the enzyme, they do not rule out these intermediates in the catalytic mechanism. The lack of binding of the s 5 T[thietane]m 3 T analog is consistent with the proposed role of 3Ј-N-3 of the pyrimidone ring in substrate binding and catalysis. The lack of binding of both thietane analogs might also be due to substantial structural differences that result from differences in the lengths of C-S and either C-O or N-O bonds (1.8 versus 1.5 Å, respectively).…”

Section: Fig 10supporting

confidence: 60%

“…Toward this end we tested the following substrates (Fig. 3A): the Dewar isomer (2) which cannot form the oxetane intermediate; the thietane analog of oxetane intermediate (5) which is in equilibrium with the s 5 -(6-4) product and predicted to be repaired efficiently; the N-methyl-3Ј-T thietane analog of the oxetane intermediate (6) which is locked in the thietane form and was predicted to be split very efficiently; and the s 5 -methyl analog of (6-4) product (4) which presumably cannot be reversed to thietane and was predicted to be refractory to photorepair.…”

Section: Resultsmentioning

confidence: 99%

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Reaction Mechanism of (6-4) Photolyase

Zhao¹,

Liu²,

Hsu³

et al. 1997

Journal of Biological Chemistry

149

167

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Section: Fig 10supporting

confidence: 60%

Section: Resultsmentioning

confidence: 99%

Reaction Mechanism of (6-4) Photolyase

Zhao¹,

Liu²,

Hsu³

et al. 1997

Journal of Biological Chemistry

149

167

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“…Interest in this fascinating subject (9-31) was triggered recently by the studies of Barton and her colleagues (9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19), which seemed to indicate the occurrence of long-range, almost distance-independent charge separation in DNA, manifesting ''chemistry at a distance'' (17). The problem of charge separation in DNA is pertinent for the realization of a particular DNA repair mechanism as an alternative to the DNA-photolyase (20)(21)(22)(23), which rests on long-range charge transfer to the defect site, i.e., a thymine dimer followed by concurrent or sequential bond breaking. Moreover, a deeper understanding of charge migration processes and of the effects of electronic excess charges localized at specific nucleic bases has wide range implications for (i) protein binding to DNA.…”

mentioning

confidence: 99%

Charge transfer and transport in DNA

Jortner

Bixon

Langenbacher

et al. 1998

Proc. Natl. Acad. Sci. U.S.A.

707

705

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We explore charge migration in DNA, advancing two distinct mechanisms of charge separation in a donor ( In 1962, Eley and Spivey proposed (1) that -interactions between stacked base pairs in double-strand DNA could provide a pathway for rapid, one-dimensional charge separation. In spite of subsequent theoretical and experimental effort in this intriguing field (2-7), experimental evidence for such ''molecular wire'' type conduction in DNA remained elusive. The studies of Warman et al. (8) in 1996 of radiation-induced conductivity in hydrated DNA argued against one-dimensional conduction confined to the base pair core. Interest in this fascinating subject (9-31) was triggered recently by the studies of Barton and her colleagues (9-19), which seemed to indicate the occurrence of long-range, almost distance-independent charge separation in DNA, manifesting ''chemistry at a distance'' (17). The problem of charge separation in DNA (9-31) is pertinent for the realization of a particular DNA repair mechanism as an alternative to the DNA-photolyase (20-23), which rests on long-range charge transfer to the defect site, i.e., a thymine dimer followed by concurrent or sequential bond breaking. Moreover, a deeper understanding of charge migration processes and of the effects of electronic excess charges localized at specific nucleic bases has wide range implications for (i) protein binding to DNA. Because electrostatic interactions are primarily responsible for the association of proteins to nucleic bases, changes in the charge density at the DNA core induced by charge separation may affect the specificity of protein binding; (ii) DNA sequencing. The control of duplex formation via charge migration may be important for specific DNA sequencing; and (iii) DNA-based biosensors. The development of biosensors, which depend on specific long-range charge separation along duplex structures in solution and preferentially at electrodes, is of considerable potential.The interpretation of the early experiments of Barton, Turro, and their colleagues (9-13) on charge separation between donor and acceptor complexes attached to DNA was fraught with some difficulties because of the possibility of aggregation effects (24). The recent data of Dandliker, Holmlin, and Barton (17-19) on hole migration between the electronically excited metal intercalator Rh(phi) 2 DMB ϩ3 and the thymine dimer, both of which are specifically incorporated in a 16-bp DNA duplex, provide evidence for long-range hole separation (over a distance scale of r ϭ 19-26 Å) with the yield being independent of donor-acceptor distance (R). These results (17)(18)(19) are in dramatic conflict with other experiments on charge separation in DNA (25-27), as well as with the standard electron transfer theory (32-40). For a donor (d)-bridge-acceptor (a) system, the theory (33-40) predicts an exponential (donor-acceptor) distance R dependence of the hole (or electron) transfer rate, k ϭ (2͞)V 2 F of the MarcusLevich-Jortner equation (33-40):Here, F is the thermally averaged n...

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“…Consequently, in the present study, we examined the splitting of the (64) photoproduct in the case of the radical cation ( Figure 2B) to search other efficient pathways, although the electron transfer from the TT lesion to the cofactor FAD has been little considered except some computational examinations for the CPD 8, 12 and the (64) photoproduct. 13 If the cofactor FAD exists as the fully reduced form FADH ¹ , the excited FADH ¹ * formed by an energy transmission from the second cofactor might receive an electron from the TT lesion, 3,12,14 which results in the formation of FADH…”

Section: ¹1mentioning

confidence: 99%

Computational Study on the Mechanism of the Electron-Transfer-Induced Repair of the (6–4) T–T Photoproduct of DNA by Photolyase: Possibility of a Radical Cation Pathway

Matsubara

Araida

Hayashi

et al. 2014

Bulletin of the Chemical Society of Japan

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The oxetane and the non-oxetane mechanisms of the electron-transfer-driven repair of the (64) TT photolesion of DNA by photolyase are examined by density functional theory (B3LYP). We calculated the radical cation pathway in addition to the radical anion and the neutral pathways for both mechanisms in order to assess the possibility of the radical cation pathway, because relatively large energy barriers have been found for the radical anion pathway. As a result, the radical anion pathway showed a large energy barrier in both the oxetane and the non-oxetane mechanisms in agreement with previous calculations. However, it was found that the radical cation pathway of the oxetane mechanism has a realistic low energy barrier. This advantage of the radical cation pathway was ascribed to the position of the radical before the formation of the oxetane and the stability of the oxetane in energy.DNA is highly a reactive substance and is therefore readily influenced and damaged, because the inside of the cell is under chemically active conditions due to ultraviolet rays, chemical substances, and so on. In fact, DNA is routinely damaged and various types of DNA lesions are known.1 Dimerized adjacent thymines, classified as single-strand damage, is also one of such DNA lesions. Although DNA lesions can be an origin of diseases such as cancer, damaged DNA is immediately recovered through a repair process 1 in order to maintain normal genetic information.For example, formed thymine dimer is repaired by photolyase under photoirradiation in plants and bacteria.2 Many people have focused on this repair process as a model and have endeavored to understand its mechanism.3 There exist two forms of thymine dimer, cyclobutane pyrimidine dimer (CPD) and (64) photoproduct (Figure 1), and many examinations of the repair mechanism have been conducted especially for the case of CPD. Photolyase is a flavoprotein that has a chromophore cofactor flavin adenine dinucleotide (FAD) (Figure 1) playing an important role as a coenzyme. A second chromophore cofactor that functions as an antenna harvesting blue light, methenyltetrahydrofolate (MTHF) or , is also present inside the protein. The FAD, which is thought to be fully reduced to FADH ¹ inside the protein, is buried in the vicinity of the active site. On the other hand, the second cofactor is further deeply buried and a little far from FAD.The generally proposed mechanism of the repair reaction of the thymine dimer on the basis of previous findings for CPD is displayed in Figure 2A. The function of the photolyase originates in the blue-light harvest by the second chromophore cofactor. The electronic state of the second cofactor that absorbed the light is enhanced to an excited state and this excitation energy is transmitted to the other cofactor FADH

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Photoenzymic repair of UV-damaged DNA: a chemist's perspective

Cited by 166 publications

References 16 publications

Reaction Mechanism of (6-4) Photolyase

Reaction Mechanism of (6-4) Photolyase

Charge transfer and transport in DNA

Computational Study on the Mechanism of the Electron-Transfer-Induced Repair of the (6–4) T–T Photoproduct of DNA by Photolyase: Possibility of a Radical Cation Pathway

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