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Johnstephen Taylor - One of the best experts on this subject based on the ideXlab platform.
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photocrosslinking of human telomeric g quadruplex loops by anti cyclobutane Thymine Dimer formation
Proceedings of the National Academy of Sciences of the United States of America, 2009Co-Authors: Dian G T Su, Huafeng Fang, Michael L Gross, Johnstephen TaylorAbstract:The unusual structural forms of telomere DNA, which protect the ends of chromosomes during replication, may render it vulnerable to unprecedented photodamage, possibly involving nonadjacent bases that are made proximate by folding. The G-quadruplex for the human telomere sequence consisting of a repeating d(TTAGGG) is one unusual form. Tel22, d[AGGG(TTAGGG)3], forms a basket structure in the presence of Na+ and may form multiple equilibrating structures in the presence of K+ with hybrid-type structures predominating. UVB irradiation of d[AGGG(TTAGGG)3] in the presence of Na+ results in a cis,syn Thymine Dimer between two adjacent Ts in a TTA loop and a mixture of nonadjacent anti Thymine Dimers between various loops. Irradiation in the presence of K+, however, produces, in addition to these same products, a large amount of specific anti Thymine Dimers formed between either T in loop 1 and the central T in loop 3. These latter species were not observed in the presence of Na+. Interloop-specific anti Thymine Dimers are incompatible with hybrid-type structures, but could arise from a chair or basket-type structure or from triplex intermediates involved in interconverting these structures. If these unique nonadjacent anti Thymine Dimer photoproducts also form in vivo, they would constitute a previously unrecognized type of DNA photodamage that may interfere with telomere replication and present a unique challenge to DNA repair. Furthermore, these unusual anti photoproducts may be used to establish the presence of G-quadruplex or quadruplex-like structures in vivo.
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structure determination of an interstrand type cis anti cyclobutane Thymine Dimer produced in high yield by uvb light in an oligodeoxynucleotide at acidic ph
Journal of the American Chemical Society, 2008Co-Authors: Dian G T Su, Michael L Gross, Johnstephen TaylorAbstract:UVB irradiation of DNA produces photoDimers in adjacent DNA bases and on rare occasions in non-adjacent bases. UVB irradiation (312 nm) of d(GTATCATGAGGTGC) gave rise to an unknown DNA photoproduct in approximately 40% yield at acidic pH of about 5. This product has a much shorter retention time in reverse phase HPLC compared to known dipyrimidine photoproducts of this sequence. A large upfield shift of two Thymine H6 NMR signals and photoreversion to the parent ODN upon irradiation with 254 nm light indicates that the photoproduct is a cyclobutane Thymine Dimer. Exonuclease-coupled MS assay establishes that the photoDimer forms between T2 and T7, which was confirmed by tandem mass spectrometric MS/MS identification of the endonuclease P1 digestion product d(T2[A3])=pd(T7[G8]). Acidic hydrolysis of the photoproduct gave a product with the same retention time on reverse phase HPLC and the same MS/MS fragmentation pattern as authentic Thy[c,a]Thy. 2D NOE NMR data are consistent with a cis-anti cyclobutane Dimer between the 3′-sides of T2 and T7 in anti glycosyl conformations that had to have arisen from an inter-stand type reaction. In addition to pH-dependent, the photoproduct yield is highly sequence specific and concentration dependent, indicating that it results from a higher order folded structure. The efficient formation of this inter-strand-type photoproduct suggests the existence of a new type of folding motif and the possibility that this type of photoproduct might also form in other folded structures, such as G-quadruplexes and i-motif structures which can be now studied by the methods described.
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synthesis and characterization of a 3 15n labeled cis syn Thymine Dimer containing dna duplex
Journal of Organic Chemistry, 2006Co-Authors: H M Bdour, Johnstephen TaylorAbstract:Cis-syn Thymine Dimers are the major photoproducts of DNA and are the principal cause of mutations induced by sunlight. To better understand the nature of base pairing with cis-syn Thymine Dimers, we have synthesized a decamer oligodeoxynucleotide (ODN) containing a cis-syn Thymine Dimer labeled at the N3 of both T's with 15N by two efficient routes from [3-15N]-thymidine phosphoramidite. In the postsynthetic irradiation route, an ODN containing an adjacent pair of [3-15N]-labeled T's was irradiated and the cis-syn Dimer-containing ODN isolated by HPLC. In the mixed building block route, a mixture of cis-syn and trans-syn Dimer-containing ODNs was synthesized from a mixture of [3-15N]-labeled Thymine Dimer phosphoramidites after which the cis-syn Dimer-containing ODN was isolated by HPLC. The N3-nitrogen and imino proton signals of an 15N-labeled Thymine Dimer-containing decamer duplex were assigned by 2D 1H−15N heterocorrelated HSQC NMR spectroscopy, and the 15N−1H coupling constant was found to be 1.8 H...
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evidence for watson crick and not hoogsteen or wobble base pairing in the selection of nucleotides for insertion opposite pyrimidines and a Thymine Dimer by yeast dna pol η
Biochemistry, 2005Co-Authors: Hanshin Hwang, Johnstephen TaylorAbstract:We have recently reported that pyrene nucleotide is preferentially inserted opposite an abasic site, the 3‘-T of a Thymine Dimer, and most undamaged bases by yeast DNA polymerase η (pol η). Because pyrene is a nonpolar molecule with no H-bonding ability, the unusually high efficiencies of dPMP insertion are ascribed to its superior base stacking ability, and underscore the importance of base stacking in the selection of nucleotides by pol η. To investigate the role of H-bonding and base pair geometry in the selection of nucleotides by pol η, we determined the insertion efficiencies of the base-modified nucleotides 2,6-diaminopurine, 2-aminopurine, 6-chloropurine, and inosine which would make a different number of H-bonds with the template base depending on base pair geometry. Watson−Crick base pairing appears to play an important role in the selection of nucleotide analogues for insertion opposite C and T as evidenced by the decrease in the relative insertion efficiencies with a decrease in the number of ...
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yeast pol η holds a cis syn Thymine Dimer loosely in the active site during elongation opposite the 3 t of the Dimer but tightly opposite the 5 t
Biochemistry, 2003Co-Authors: Kaijiang Zhang, Lilly Zhou, Paul Hohler, Eric T Kool, Fenghua Yuan, Zhigang Wang, Johnstephen TaylorAbstract:Polymerase is a member of the Y family of DNA polymerases which is able to bypass Thymine Dimers efficiently and in a relatively error-free manner. To elucidate the mechanism of Dimer bypass, the efficiency of dAMP and pyrene nucleotide insertion opposite the Thymine Dimer and its N3- methyl derivatives was determined. Pol inserts pyrene nucleotide with greater efficiency than dAMP opposite the 3'-T of an unDimerized or Dimerized T and is an effective inhibitor of DNA synthesis by pol . Substitution of the N3H of the 3'-T of an unDimerized T or a Dimerized T with a methyl group has little effect on the insertion efficiency of pyrene nucleotide but greatly inhibits the insertion of dAMP. Together, these results suggest that the error-free insertion of dAMP opposite the 3 '-T of the cis-syn Thymine Dimer happens by way of a loosely held Dimer in the active site which can be displaced from the active site by pyrene nucleotide. In contrast, pol cannot insert pyrene nucleotide opposite the 5'-T of the Dimer, whereas it can insert dAMP with efficiency comparable to that opposite the 3'-T. The inability to insert pyrene nucleotide opposite the 5'-T of the Dimer is consistent with the idea that while the polymerase binds loosely to a templating nucleotide, it binds tightly to the nucleotide to its 3 '-side. Overall, the results show a marked difference from similar studies on pol I family polymerases, and suggest mechanisms by which this Y family polymerase can process damaged DNA efficiently.
Dongping Zhong - One of the best experts on this subject based on the ideXlab platform.
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dynamics and mechanism of uv damaged dna repair in indole Thymine Dimer adduct molecular origin of low repair quantum efficiency
Journal of Physical Chemistry B, 2015Co-Authors: Qinhua Song, Lijuan Wang, Dongping ZhongAbstract:Many biomimetic chemical systems for repair of UV-damaged DNA showed very low repair efficiency, and the molecular origin is still unknown. Here, we report our systematic characterization of the repair dynamics of a model compound of indole–Thymine Dimer adduct in three solvents with different polarity. By resolving all elementary steps including three electron-transfer processes and two bond-breaking and bond-formation dynamics with femtosecond resolution, we observed the slow electron injection in 580 ps in water, 4 ns in acetonitrile, and 1.38 ns in dioxane, the fast back electron transfer without repair in 120, 150, and 180 ps, and the slow bond splitting in 550 ps, 1.9 ns, and 4.5 ns, respectively. The Dimer bond cleavage is clearly accelerated by the solvent polarity. By comparing with the biological repair machine photolyase with a slow back electron transfer (2.4 ns) and a fast bond cleavage (90 ps), the low repair efficiency in the biomimetic system is mainly determined by the fast back electron ...
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dynamics and mechanism of uv damaged dna repair in indole Thymine Dimer adduct molecular origin of low repair quantum efficiency b
The Journal of Physical Chemistry, 2015Co-Authors: Qinhua Song, Lijuan Wang, Dongping ZhongAbstract:Many biomimetic chemical systems for repair of UV-damaged DNA showed very low repair efficiency, and the molecular origin is still unknown. Here, we report our systematic characterization of the repair dynamics of a model compound of indole–Thymine Dimer adduct in three solvents with different polarity. By resolving all elementary steps including three electron-transfer processes and two bond-breaking and bond-formation dynamics with femtosecond resolution, we observed the slow electron injection in 580 ps in water, 4 ns in acetonitrile, and 1.38 ns in dioxane, the fast back electron transfer without repair in 120, 150, and 180 ps, and the slow bond splitting in 550 ps, 1.9 ns, and 4.5 ns, respectively. The Dimer bond cleavage is clearly accelerated by the solvent polarity. By comparing with the biological repair machine photolyase with a slow back electron transfer (2.4 ns) and a fast bond cleavage (90 ps), the low repair efficiency in the biomimetic system is mainly determined by the fast back electron transfer and slow bond breakage. We also found that the model system exists in a dynamic heterogeneous C-clamped conformation, leading to a stretched dynamic behavior. In water, we even identified another stacked form with ultrafast cyclic electron transfer, significantly reducing the repair efficiency. Thus, the comparison of the repair efficiency in different solvents is complicated and should be cautious, and only the dynamics by resolving all elementary steps can finally determine the total repair efficiency. Finally, we use the Marcus electron-transfer theory to analyze all electron-transfer reactions and rationalize all observed electron-transfer dynamics.
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dynamics and mechanism of dna repair in a biomimetic system flavin Thymine Dimer adduct
Journal of the American Chemical Society, 2012Co-Authors: Qinhua Song, Chaitanya Saxena, Lijuan Wang, Dongping ZhongAbstract:To mimic photolyase for efficient repair of UV-damaged DNA, numerous biomimetic systems have been synthesized, but all show low repair efficiency. The molecular mechanism of this low-efficiency process is still poorly understood. Here we report our direct mapping of the repair processes of a flavin–Thymine Dimer adduct with femtosecond resolution. We followed the entire dynamic evolution and observed direct electron transfer (ET) from the excited flavin to the Thymine Dimer in 79 ps. We further observed two competitive pathways, productive Dimer ring splitting within 435 ps and futile back-ET in 95 ps. Our observations reveal that the underlying mechanism for the low repair quantum yield of flavin–Thymine Dimer adducts is the short-lived excited flavin moiety and the fast dynamics of futile back-ET without repair.
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Dynamics and Mechanism of DNA Repair in a Biomimetic System: Flavin–Thymine Dimer Adduct
Journal of the American Chemical Society, 2012Co-Authors: Qinhua Song, Chaitanya Saxena, Lijuan Wang, Dongping ZhongAbstract:To mimic photolyase for efficient repair of UV-damaged DNA, numerous biomimetic systems have been synthesized, but all show low repair efficiency. The molecular mechanism of this low-efficiency process is still poorly understood. Here we report our direct mapping of the repair processes of a flavin–Thymine Dimer adduct with femtosecond resolution. We followed the entire dynamic evolution and observed direct electron transfer (ET) from the excited flavin to the Thymine Dimer in 79 ps. We further observed two competitive pathways, productive Dimer ring splitting within 435 ps and futile back-ET in 95 ps. Our observations reveal that the underlying mechanism for the low repair quantum yield of flavin–Thymine Dimer adducts is the short-lived excited flavin moiety and the fast dynamics of futile back-ET without repair.
Qinhua Song - One of the best experts on this subject based on the ideXlab platform.
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dynamics and mechanism of uv damaged dna repair in indole Thymine Dimer adduct molecular origin of low repair quantum efficiency
Journal of Physical Chemistry B, 2015Co-Authors: Qinhua Song, Lijuan Wang, Dongping ZhongAbstract:Many biomimetic chemical systems for repair of UV-damaged DNA showed very low repair efficiency, and the molecular origin is still unknown. Here, we report our systematic characterization of the repair dynamics of a model compound of indole–Thymine Dimer adduct in three solvents with different polarity. By resolving all elementary steps including three electron-transfer processes and two bond-breaking and bond-formation dynamics with femtosecond resolution, we observed the slow electron injection in 580 ps in water, 4 ns in acetonitrile, and 1.38 ns in dioxane, the fast back electron transfer without repair in 120, 150, and 180 ps, and the slow bond splitting in 550 ps, 1.9 ns, and 4.5 ns, respectively. The Dimer bond cleavage is clearly accelerated by the solvent polarity. By comparing with the biological repair machine photolyase with a slow back electron transfer (2.4 ns) and a fast bond cleavage (90 ps), the low repair efficiency in the biomimetic system is mainly determined by the fast back electron ...
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dynamics and mechanism of uv damaged dna repair in indole Thymine Dimer adduct molecular origin of low repair quantum efficiency b
The Journal of Physical Chemistry, 2015Co-Authors: Qinhua Song, Lijuan Wang, Dongping ZhongAbstract:Many biomimetic chemical systems for repair of UV-damaged DNA showed very low repair efficiency, and the molecular origin is still unknown. Here, we report our systematic characterization of the repair dynamics of a model compound of indole–Thymine Dimer adduct in three solvents with different polarity. By resolving all elementary steps including three electron-transfer processes and two bond-breaking and bond-formation dynamics with femtosecond resolution, we observed the slow electron injection in 580 ps in water, 4 ns in acetonitrile, and 1.38 ns in dioxane, the fast back electron transfer without repair in 120, 150, and 180 ps, and the slow bond splitting in 550 ps, 1.9 ns, and 4.5 ns, respectively. The Dimer bond cleavage is clearly accelerated by the solvent polarity. By comparing with the biological repair machine photolyase with a slow back electron transfer (2.4 ns) and a fast bond cleavage (90 ps), the low repair efficiency in the biomimetic system is mainly determined by the fast back electron transfer and slow bond breakage. We also found that the model system exists in a dynamic heterogeneous C-clamped conformation, leading to a stretched dynamic behavior. In water, we even identified another stacked form with ultrafast cyclic electron transfer, significantly reducing the repair efficiency. Thus, the comparison of the repair efficiency in different solvents is complicated and should be cautious, and only the dynamics by resolving all elementary steps can finally determine the total repair efficiency. Finally, we use the Marcus electron-transfer theory to analyze all electron-transfer reactions and rationalize all observed electron-transfer dynamics.
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dynamics and mechanism of dna repair in a biomimetic system flavin Thymine Dimer adduct
Journal of the American Chemical Society, 2012Co-Authors: Qinhua Song, Chaitanya Saxena, Lijuan Wang, Dongping ZhongAbstract:To mimic photolyase for efficient repair of UV-damaged DNA, numerous biomimetic systems have been synthesized, but all show low repair efficiency. The molecular mechanism of this low-efficiency process is still poorly understood. Here we report our direct mapping of the repair processes of a flavin–Thymine Dimer adduct with femtosecond resolution. We followed the entire dynamic evolution and observed direct electron transfer (ET) from the excited flavin to the Thymine Dimer in 79 ps. We further observed two competitive pathways, productive Dimer ring splitting within 435 ps and futile back-ET in 95 ps. Our observations reveal that the underlying mechanism for the low repair quantum yield of flavin–Thymine Dimer adducts is the short-lived excited flavin moiety and the fast dynamics of futile back-ET without repair.
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Dynamics and Mechanism of DNA Repair in a Biomimetic System: Flavin–Thymine Dimer Adduct
Journal of the American Chemical Society, 2012Co-Authors: Qinhua Song, Chaitanya Saxena, Lijuan Wang, Dongping ZhongAbstract:To mimic photolyase for efficient repair of UV-damaged DNA, numerous biomimetic systems have been synthesized, but all show low repair efficiency. The molecular mechanism of this low-efficiency process is still poorly understood. Here we report our direct mapping of the repair processes of a flavin–Thymine Dimer adduct with femtosecond resolution. We followed the entire dynamic evolution and observed direct electron transfer (ET) from the excited flavin to the Thymine Dimer in 79 ps. We further observed two competitive pathways, productive Dimer ring splitting within 435 ps and futile back-ET in 95 ps. Our observations reveal that the underlying mechanism for the low repair quantum yield of flavin–Thymine Dimer adducts is the short-lived excited flavin moiety and the fast dynamics of futile back-ET without repair.
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efficient photosensitized splitting of the Thymine Dimer oxetane unit on its modifying β cyclodextrin by a binding electron donor
Organic and Biomolecular Chemistry, 2006Co-Authors: Wenjian Tang, Qinhua Song, Hongbo Wang, Jingyu YuAbstract:Two modified β-cyclodextrins (β-CDs) with a Thymine Dimer and a Thymine oxetane adduct respectively, TD-CD and Ox-CD, have been prepared, and utilized to bind an electron-rich chromophore, indole or N,N-dimethylaniline (DMA), to form a supramolecular complex. We have examined the photosensitized splitting of the Dimer/oxetane unit in TD-CD/Ox-CD by indole or DMA via an electron-transfer pathway, and observed high splitting efficiencies of the Dimer/oxetane unit. On the basis of measurements of fluorescence spectra and splitting quantum yields, it is suggested that the splitting reaction occurs in a supramolecular complex by an inclusion interaction between the modified β-CDs and DMA or indole. The back electron transfer, which leads low splitting efficiencies for the covalently-linked chromophore–Dimer/oxetane compounds, is suppressed in the non-covalently-bound complex, and the mechanism has been discussed.
Aziz Sancar - One of the best experts on this subject based on the ideXlab platform.
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recognition and repair of the cyclobutane Thymine Dimer a major cause of skin cancers by the human excision nuclease
Genes & Development, 2003Co-Authors: Joyce T Reardon, Aziz SancarAbstract:The cyclobutane Thymine Dimer is the major DNA lesion induced in human skin by sunlight and is a primary cause of skin cancer, the most prevalent form of cancer in the Northern Hemisphere. In humans, the only known cellular repair mechanism for eliminating the Dimer from DNA is nucleotide excision repair. Yet the mechanism by which the Dimer is recognized and removed by this repair system is not known. Here we demonstrate that the six-factor human excision nuclease recognizes and removes the Dimer at a rate consistent with the in vivo rate of removal of this lesion, even though none of the six factors alone is capable of efficiently discriminating the Dimer from undamaged DNA. We propose a recognition mechanism by which the low-specificity recognition factors, RPA, XPA, and XPC, act in a cooperative manner to locate the lesion and, aided by the kinetic proofreading provided by TFIIH, form a high-specificity complex at the damage site that initiates removal of Thymine Dimers at a physiologically relevant rate and specificity.
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human transcription release factor 2 dissociates rna polymerases i and ii stalled at a cyclobutane Thymine Dimer
Journal of Biological Chemistry, 1999Co-Authors: Ryujiro Hara, Christopher P Selby, David Price, Aziz SancarAbstract:Abstract RNA polymerase II stalled at a lesion in the transcribed strand is thought to constitute a signal for transcription-coupled repair. Transcription factors that act on RNA polymerase in elongation mode potentially influence this mode of repair. Previously, it was shown that transcription elongation factors TFIIS and Cockayne’s syndrome complementation group B protein did not disrupt the ternary complex of RNA polymerase II stalled at a Thymine cyclobutane Dimer, nor did they enable RNA polymerase II to bypass the Dimer. Here we investigated the effect of the transcription factor 2 on RNA polymerase II and RNA polymerase I stalled at Thymine Dimers. Transcription factor 2 is known to release transcripts from RNA polymerase II early elongation complex generated by pulse-transcription. We found that factor 2 (which is also called release factor) disrupts the ternary complex of RNA polymerase II at a Thymine Dimer and surprisingly exerts the same effect on RNA polymerase I. These findings show that in mammalian cells a RNA polymerase I or RNA polymerase II transcript truncated by a lesion in the template strand may be discarded unless repair is accomplished rapidly by a mechanism that does not displace stalled RNA polymerases.
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rna polymerase ii stalled at a Thymine Dimer footprint and effect on excision repair
Nucleic Acids Research, 1997Co-Authors: Christopher P Selby, Ronny Drapkin, Danny Reinberg, Aziz SancarAbstract:: Bulky lesions in the template strand block the progression of RNA polymerase II (RNAP II) and are repaired more rapidly than lesions in the non-transcribed strand, which do not block transcription. In order to better understand the basis of this transcription-coupled repair we developed an in vitro system with purified transcription and nucleotide excision repair proteins and a plasmid containing the adenovirus major late promoter and a Thymine Dimer in the template strand downstream of the transcription start site. The footprint of RNAP II stalled at the Thymine Dimer, obtained using DNase I, lambda exonuclease and T4 polymerase 3'-->5'exonuclease, covers approximately 40 nt and is nearly symmetrical around the Dimer. The ternary complex formed at the lesion site is rather stable, with a half-life of approximately 20 h. Surprisingly, addition of human repair proteins results in repair of transcription-blocking Dimers in the ternary complex. The blocked polymerase neither inhibits nor stimulates repair and repair is observed in the absence of CSB protein, the putative human transcription-repair coupling factor.
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dna photolyase repairs the trans syn cyclobutane Thymine Dimer
Biochemistry, 1993Co-Authors: Khushbeer Malhotra, Johnstephen Taylor, Colin A Smith, Aziz SancarAbstract:DNA photolyases catalyze the splitting of the cyclobutane ring joining the two dihydropyrimidines of a pyrimidine Dimer by a photoinduced electron-transfer reaction. Previous studies concluded that photolyase repairs only the cis-syn form of the eight stereoisomers of the cyclobutane pyrimidine Dimer (Pyr( IPyr). In this study we found that Escherichia coli photolyase binds to the trans-syn-I isomer of T( IT with about 1 04-fold lower affinity than the cis-syn isomer but it repairs it relatively efficiently.
Lijuan Wang - One of the best experts on this subject based on the ideXlab platform.
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dynamics and mechanism of uv damaged dna repair in indole Thymine Dimer adduct molecular origin of low repair quantum efficiency
Journal of Physical Chemistry B, 2015Co-Authors: Qinhua Song, Lijuan Wang, Dongping ZhongAbstract:Many biomimetic chemical systems for repair of UV-damaged DNA showed very low repair efficiency, and the molecular origin is still unknown. Here, we report our systematic characterization of the repair dynamics of a model compound of indole–Thymine Dimer adduct in three solvents with different polarity. By resolving all elementary steps including three electron-transfer processes and two bond-breaking and bond-formation dynamics with femtosecond resolution, we observed the slow electron injection in 580 ps in water, 4 ns in acetonitrile, and 1.38 ns in dioxane, the fast back electron transfer without repair in 120, 150, and 180 ps, and the slow bond splitting in 550 ps, 1.9 ns, and 4.5 ns, respectively. The Dimer bond cleavage is clearly accelerated by the solvent polarity. By comparing with the biological repair machine photolyase with a slow back electron transfer (2.4 ns) and a fast bond cleavage (90 ps), the low repair efficiency in the biomimetic system is mainly determined by the fast back electron ...
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dynamics and mechanism of uv damaged dna repair in indole Thymine Dimer adduct molecular origin of low repair quantum efficiency b
The Journal of Physical Chemistry, 2015Co-Authors: Qinhua Song, Lijuan Wang, Dongping ZhongAbstract:Many biomimetic chemical systems for repair of UV-damaged DNA showed very low repair efficiency, and the molecular origin is still unknown. Here, we report our systematic characterization of the repair dynamics of a model compound of indole–Thymine Dimer adduct in three solvents with different polarity. By resolving all elementary steps including three electron-transfer processes and two bond-breaking and bond-formation dynamics with femtosecond resolution, we observed the slow electron injection in 580 ps in water, 4 ns in acetonitrile, and 1.38 ns in dioxane, the fast back electron transfer without repair in 120, 150, and 180 ps, and the slow bond splitting in 550 ps, 1.9 ns, and 4.5 ns, respectively. The Dimer bond cleavage is clearly accelerated by the solvent polarity. By comparing with the biological repair machine photolyase with a slow back electron transfer (2.4 ns) and a fast bond cleavage (90 ps), the low repair efficiency in the biomimetic system is mainly determined by the fast back electron transfer and slow bond breakage. We also found that the model system exists in a dynamic heterogeneous C-clamped conformation, leading to a stretched dynamic behavior. In water, we even identified another stacked form with ultrafast cyclic electron transfer, significantly reducing the repair efficiency. Thus, the comparison of the repair efficiency in different solvents is complicated and should be cautious, and only the dynamics by resolving all elementary steps can finally determine the total repair efficiency. Finally, we use the Marcus electron-transfer theory to analyze all electron-transfer reactions and rationalize all observed electron-transfer dynamics.
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dynamics and mechanism of dna repair in a biomimetic system flavin Thymine Dimer adduct
Journal of the American Chemical Society, 2012Co-Authors: Qinhua Song, Chaitanya Saxena, Lijuan Wang, Dongping ZhongAbstract:To mimic photolyase for efficient repair of UV-damaged DNA, numerous biomimetic systems have been synthesized, but all show low repair efficiency. The molecular mechanism of this low-efficiency process is still poorly understood. Here we report our direct mapping of the repair processes of a flavin–Thymine Dimer adduct with femtosecond resolution. We followed the entire dynamic evolution and observed direct electron transfer (ET) from the excited flavin to the Thymine Dimer in 79 ps. We further observed two competitive pathways, productive Dimer ring splitting within 435 ps and futile back-ET in 95 ps. Our observations reveal that the underlying mechanism for the low repair quantum yield of flavin–Thymine Dimer adducts is the short-lived excited flavin moiety and the fast dynamics of futile back-ET without repair.
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Dynamics and Mechanism of DNA Repair in a Biomimetic System: Flavin–Thymine Dimer Adduct
Journal of the American Chemical Society, 2012Co-Authors: Qinhua Song, Chaitanya Saxena, Lijuan Wang, Dongping ZhongAbstract:To mimic photolyase for efficient repair of UV-damaged DNA, numerous biomimetic systems have been synthesized, but all show low repair efficiency. The molecular mechanism of this low-efficiency process is still poorly understood. Here we report our direct mapping of the repair processes of a flavin–Thymine Dimer adduct with femtosecond resolution. We followed the entire dynamic evolution and observed direct electron transfer (ET) from the excited flavin to the Thymine Dimer in 79 ps. We further observed two competitive pathways, productive Dimer ring splitting within 435 ps and futile back-ET in 95 ps. Our observations reveal that the underlying mechanism for the low repair quantum yield of flavin–Thymine Dimer adducts is the short-lived excited flavin moiety and the fast dynamics of futile back-ET without repair.