The effect of thymine dimers on DNA: DNA hybridization

Kahn, Michael L.

doi:10.1002/bip.1974.360130403

Cited by 18 publications

(6 citation statements)

References 16 publications

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“…This may explain why at certain template positions where the DNA⅐DNA hybrid at the leading edge of the transcription bubble is energetically favored over the RNA⅐DNA hybrid, as in the case of dA⅐dT base pairing versus dA⅐rU base pairing, RNAP becomes efficiently arrested at these sequences in the nontemplate strand. Conversely, the presence of a CPD in this sequence context may shift the equilibrium toward the RNA⅐DNA hybrid rather than the DNA⅐DNA hybrid (31). This is also in agreement with our previous observation that a CPD is not inherently a block to RNAP II when it is located in the nontranscribed strand (22).…”

Section: Characterization Of a 42-mer Dna Sequence Containing Thesupporting

confidence: 91%

Nucleotide Sequence Context Effect of a Cyclobutane Pyrimidine Dimer upon RNA Polymerase II Transcription

Tornaletti

Donahue

Reines

et al. 1997

Journal of Biological Chemistry

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We have studied the role of sequence context upon RNA polymerase II arrest by a cyclobutane pyrimidine dimer using an in vitro transcription system consisting of templates containing a specifically located cyclobutane pyrimidine dimer (CPD) and purified RNA polymerase II (RNAP II) and initiation factors. We selected a model sequence containing a well characterized site for RNAP II arrest in vitro, the human histone H3.3 gene arrest site. The 13-base pair core of the arrest sequence contains two runs of T in the nontranscribed strand that impose a bend in the DNA. We hypothesized that arrest of RNAP II might be affected by the presence of a CPD, based upon the observation that a CPD located at the center of a dA 6 ⅐dT 6 tract eliminates bending (Wang, C.-I., and Taylor, J.-S. (1991) Proc. Natl. Acad. Sci. U. S. A. 88, 9072-9076). We examined the normal H3.3 sequence and a mutant sequence containing a T 3 G transversion, which reduces bending and efficiency of arrest. We show that a CPD in the transcribed strand at either of two locations in the arrest site is a potent block to transcription. However, a CPD in the nontranscribed strand only transiently pauses RNAP II. The CPD in concert with a mutation in the arrest site can reduce the extent of bending of the DNA and improve readthrough efficiency. These results demonstrate the potential importance of sequence context for the effect of CPDs within transcribed sequences.DNA repair rates along the genome are clearly heterogeneous (2). Certain lesions in actively transcribed genes are repaired much faster than in inactive loci. This can be generally ascribed to the preferential repair of the transcribed strand over the nontranscribed strand (3). Transcription-dependent repair has been shown to occur in mammalian cells (4, 5), in Escherichia coli (6), and in Saccharomyces cerevisiae (7-9), suggesting that it is a widespread phenomenon reflecting the existence of a mechanism that directly couples nucleotide excision repair and transcription.An additional level of repair heterogeneity is represented by the sequence-specific rates of repair of UV-induced cyclobutane pyrimidine dimers (CPDs) 1 (10 -13). Analysis of repair of CPDs along the tumor suppressor gene p53 (11) revealed that the sites at which CPDs were poorly repaired were also hot spots for mutations found in skin cancers, demonstrating a direct correlation between slow repair of CPDs and mutation hot spots in skin cancer. A correlation between slow repair rates and occurrence of mutations has also been observed in the hypoxanthine-guanine phosphoribosyltransferase gene in human fibroblasts treated with benzo[a]pyrene diol epoxide (14). Slow repair of CPDs at particular sites on the transcribed strand (10, 11) may reflect efficient bypass of CPDs by RNA polymerase II (RNAP II) in specific sequence contexts. A dimer might even be masked in particular sequence contexts such that transcription-coupled repair would not be initiated.The role of the sequence context of a lesion on transcription can be analyzed more ...

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Section: Characterization Of a 42-mer Dna Sequence Containing Thesupporting

confidence: 91%

Nucleotide Sequence Context Effect of a Cyclobutane Pyrimidine Dimer upon RNA Polymerase II Transcription

Tornaletti

Donahue

Reines

et al. 1997

Journal of Biological Chemistry

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“…The UV exposure rate was such to gencrate 0.167 PD per PAT 153 molecule per s. Ag' was removed by dialyzing once against one liter of 0.02 M KCN. then twice against one liter of 0.12 Msodium phosphate (pH 7.4) (Kahn. 1974) and twice against SO0 m t of 10 mM Tris-HCI ( p H 8.0).…”

Section: Methodsmentioning

confidence: 99%

“…The conditions of irradiation allow other considerations. 254 nm radiation mediates photochemical reactions of thymine and cytosine (Varghese, 1971) while DNA sensitization in the presence of Agf seems to excite thymine only (Kahn and Landry, 1973;Kahn, 1974). In addition, the rate of dimer formation is greatly increased by the presence of Ag+ during irradiation.…”

Section: Disc~ssionmentioning

confidence: 99%

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IRRADIATION OF CIRCULAR DNA WITH 254 nm RADIATION OR SENSITIZATION IN THE PRESENCE OF Ag+ EVIDENCE FOR UNWINDING BY PHOTOPRODUCTS OTHER THAN PYRIMIDINE DIMERS

Ciarrocchi

Sutherland

1983

Photochem & Photobiology

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Abstract— Structural alterations of DNA irradiated with UV light were analyzed by the agarose gel technique. Relaxed, circular pAT 153 DNA molecules were sensitized by broad band radiation with a maximum at 313 nm in the presence of silver ions or irradiated with 254 nm light in buffer only. In both cases the electrophoretic mobility of DNA topoisomers was altered as a linear function of UV exposure. For DNA irradiated in the sensitized reaction the unwinding angle per site sensitive to Micrococcus luteus pyrimidine dimer endonuclease was found tobe–11.4°. This value is significantly smaller thanthe–14.3° already known for DNA topoisomers irradiated with 254 nm light. The irradiated DNAs were a very good substrate for the Escherichia coli photoreactivating enzyme (PRE). However, the photoenzymic removal of all sites sensitive to the endonuclease specific for pyrimidine dimers was not coupled to a full restoration of the original electrophoretic mobility. Thirty and 23% of the unwinding were still present in the photoreactivated topoisomers and the unwinding angles per pyrimidine dimer were then recalculatedas–10.1°and–8.7° for DNAs irradiated with 254 nm and sensitized, respectively. The limited difference between these two values could result from the different base composition of the pyrimidine dimers generated in the conditions of irradiation used. These results show that the tertiary structure of DNA is measureably altered by UV photodamages other than pyrimidine dimers.

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“…Their importance in the photochemistry of DNA remains to be determined. The damages induced by direct or photosensitized irradiation of DNA have been examined using different approaches [29,39,40,62,SO]. No evidence for clustering of Thy dimers was found by the formaldehyde method [38], thus ruling out longrange energy transfer.…”

Section: Photochemistry Of Nucleic Acidsmentioning

confidence: 99%

Excited States of Nucleic Acids

Favre

Vigny

1975

Photochem & Photobiology

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The literature on the electronic excited states of nucleic acids is reviewed covering the period approximately of mid 1973-mid 1975. Our interest focuses on the nucleic acids themselves as well as on their components and derivatives from two points of view which are closely related: (i) their spectroscopic properties, and (ii) their photochemical properties. The photobiological aspects of nucleic acids will not be considered here, however. Spectroscopy of nucleic acidsVery few papers have been concerned with the investigation of the excited singlet states of nucleic acid bases at high resolution. Sharp absorption and emission spectra are reported for crystalline purine at 4 K and an interpretation of the pattern of the excited singlet states is given using molecular orbital calculations and correlations with pyrimidine and aza substituted derivatives [63]. A study of the polarized singlecrystal reflection spectra of 6-azauracil shows that the 260 nm absorption band can be resolved into two bands [S]. Higher excited singlet states of nucleic acid bases have been investigated in thin films 1911 and the energy diagrams have been evaluated both in the neutral and ionized state [SS]. Theoretical calculations of the energies of the lower-out-of-plane transitions of the nucleic acid bases, their tautomers and ions have been made using the CNDO-CI method [35]. The CND0/2 method has also been used for these molecules [ 1011 and thiouracils [25].Studies of the fluorescence and phosphorescence emission of nucleic acids in water-alcohol glasses at low temperature, where the quantum yields are high, have received less emphasis than previously. In the case of the dinucleotide C3fP5C, the fluorescence polarimtion has been interpreted in terms of a charge resonance in the excimer state [lo]. Further work has been reported on the triplet emission of DNA [45] and yeast tRNAPhe [34]. In that case, the triplet emission of Ado can be observed at 1.2 K, but not at 77 K, partially due to energy transfer to the "Y" base. Energy transfer in Ado frozen aggregates to appropriate traps has been demonstrated [49] as well as triplet-triplet energy transfer from the bases to tryptophan in oligopeptide, poly rA (or DNA) complexes [33]. The large previously observed enhancement in the phosphorescence of DNA when Agf

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The effect of thymine dimers on DNA: DNA hybridization

Cited by 18 publications

References 16 publications

Nucleotide Sequence Context Effect of a Cyclobutane Pyrimidine Dimer upon RNA Polymerase II Transcription

Nucleotide Sequence Context Effect of a Cyclobutane Pyrimidine Dimer upon RNA Polymerase II Transcription

IRRADIATION OF CIRCULAR DNA WITH 254 nm RADIATION OR SENSITIZATION IN THE PRESENCE OF Ag+ EVIDENCE FOR UNWINDING BY PHOTOPRODUCTS OTHER THAN PYRIMIDINE DIMERS

Excited States of Nucleic Acids

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