The structure of d(CGCGAAT[ ]TCGCG)-d(CGCGAATTCGCG): the incorporation of a thymine photodimer into a B-DNA helix

Rao, Shashidhar N.; Keepers, Joe W.; Koliman, Peter

doi:10.1093/nar/12.11.4789

Cited by 74 publications

(72 citation statements)

References 16 publications

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“…4b confirms that the bend occurs over several base pairs with no evidence of a kink that either occurs over one base pair or disrupts stacking. We note that other groups using similar minimization techniques have obtained conflicting results regarding a bend in DNA produced by thymine dimers (19,20). They found a bend only when DNA conformation was altered before energy minimization.…”

Section: Resultsmentioning

confidence: 71%

Spermine-DNA interactions: a theoretical study.

Feuerstein¹,

Pattabiraman²,

Marton³

1986

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

159

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Models for the interaction of spermine and DNA were studied by performing conformational energy calculations on spermine and molecular mechanics calculations on major and minor groove complexes of spermine and oligomers of DNA. Docked into the major groove of B-DNA, spermine stabilizes the complex by aimig interactions between proton acceptors on the oligomer and proton donors on spermine. This is achieved by bending the major groove of DNA over spermine and altering oligomer sugar puckering and interstrand phosphate distances. By comparison, Liquori's minor groove model appears to be less stable than the major groove model. This evidence favors a preferential binding of spermine to certain sites in DNA, which provides a powerful force for the modification of DNA conformation.Polyamines are aliphatic polycationic compounds that are found in all cells and have a significant role in the regulation of normal and malignant cell proliferation (1). Polyamine biosynthesis is highly regulated, and intracellular levels of polyamines can change rapidly by orders of magnitude when cell growth is stimulated (1). It has been proposed that polyamines affect growth by interacting with DNA. Evidence for these interactions obtained from experiments conducted in cell-free systems includes the ability of polyamines to precipitate DNA (2) and to raise the melting temperature of natural DNAs (3). Other results obtained by electron microscopy and micrococcal nuclease digestion of DNA show that polyamines can produce an organized condensed DNA structure (4). On the cellular level, depletion of intracellular polyamines by treatment with inhibitors of polyamine biosynthesis produces effects consistent with models in which polyamine interactions alter DNA conformation (5).It has been shown recently that polyamines can cause a B to Z conformational transition in both poly[d(G-m5C)] and poly[d(G-C)] (6, 7). In these studies, significant and specific changes in DNA structure can take place at low polyamine/ base-pair ratios. Differences in the ability of two spermidine analogs with the same charge but different structures to cause the B to Z transition suggest that a specific interaction causes the transition (8).Even though the interactions between DNA and polyamines have been described in detail, the molecular basis for an interaction has not been well-characterized. A major controversy in the field involves the question of whether or not the interaction is specific. In theoretical studies, polyamines have been treated as point concentrations of positive charge that interact with a DNA molecule considered to be a linear concentration of negative charge (9); in this counterion condensation model, chemical structure is ignored and specificity in interaction is not considered. Experimental results consistent with this model have been published (9)(10)(11). In other models, structures ofboth DNA and polyamines are taken into account. In one of these models, the tetracationic polyamine spermine bridges the minor groove ofDNA to give a ...

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Section: Resultsmentioning

confidence: 71%

Spermine-DNA interactions: a theoretical study.

Feuerstein¹,

Pattabiraman²,

Marton³

1986

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

159

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“…For the cis-svn dimers more conformational freedom was found and also the average structures exhibited more structural variation among themselves. A comparison with the results of earlier theoretical [27,281 and structural studies of oligonucleotides [18,29] is made. The biological implications of this structural information regarding the ultraviolet induced mutations will be discussed.…”

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confidence: 96%

NMR studies of bipyrimidine cyclobutane photodimers

Koning

Soest

Kaptein

1991

European Journal of Biochemistry

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Cyclobutane-type photodimers of dinucleoside monophosphates dCpdT, dTpdC and dTpdT were prepared by ultraviolet irradiation in the presence of acetophenone as photosensitizer. The cytosine-containing derivatives were found to deaminate forming uracil products. Using one-and two-dimensional NMR, the photoproducts were characterized as cis-syn and trans-syn cyclobutane photodimers. On the basis of NOE data the structures of the cis-syn and trans-syn products of dUpdT were determined using distance-geometry and restrained-energyminimization methods. The cis-syn structures showed (high-ANTI/SYN)/high-ANTI glycosidic linkages while the trans-syn structures were in the SYN-ANTI region. The backbone conformations of both structures were in fair agreement with the coupling-constant-data. The trans-syn structures were found to be very rigid and similar in all three products. For the three cis-syn structures more conformational freedom and more variation among the three structures was observed.Ultraviolet radiation may induce damage in living organisms. Exposure to ultraviolet light mainly results in photochemical alterations of the DNA [l]. Currently there is great interest in the relation between the photochemical lesions in DNA and the mutagenic effects of these lesions. The heterocyclic bases (purines and pyrimidines) are the photoreactive species in DNA. They strongly absorb ultraviolet light in the region 230 -290 nm. This is primarily due to n+n* transitions resulting in an absorption maximum for the bases occuring at about 260 nm. Intersystem crossing to a triplet state with lower energy turns the heterocyclic base into a chemically reactive species. Trapped in the longer-lived excited triplet state, the bases, especially the pyrimidines, can undergo several photochemical reactions [2, 31.These reactions occur primarily between two adjacent bases. The most abundant photoproducts are the cyclobutane dimers between two adjacent pyrimidine bases [4]. Of these the thymine-thymine cyclobutane dimers in oligodeoxynucleotides and poly(deoxynuc1eotides) have been most widely investigated [l, 5 -71. Other photoproducts which have been characterized are the 6 plus 4-pyrimidone/pyrimidine photoadducts [8, 91 and the pyrimidine photohydrates [lo, 111. Purine bases are much less affected by ultraviolet radiation, but recent studies have shown that the adenine bases also undergo photochemical alterations when exposed to ultraviolet light. It has been shown that photoproducts are formed in oligodeoxyadenylic and poly(deoxyadeny1ic acids) [12,13]. Also, the photodimers of the dinucleoside monophosphates dApdA and dTpdA have been isolated and characterized [14, 151.Stereochemically, cyclobutyl-linked pyrimidines may exist in four different isomeric forms, two of which are optically active and exist as enantiomers [16] (with a head-to-tail arrangement of the pyrimidine bases) can be ruled out in DNA on steric grounds. Therefore, in singlestranded and duplex DNA there are four possible cyclobutane dimers (see Fig. 1) all in the syn ...

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“…1) (23). These sites have greater rotational freedom in the phosphate backbone, which is crucial in bringing adjacent pyrimidines to the correct angle to form CPDs (27). Interestingly, when free genomic DNA containing randomly distributed CPDs is assembled into nucleosomes, the CPDs are found preferentially facing away from the histone surface ( Fig.…”

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confidence: 99%

Accommodation and Repair of a UV Photoproduct in DNA at Different Rotational Settings on the Nucleosome Surface

Svedružić

Wang²,

Kosmoski³

et al. 2005

Journal of Biological Chemistry

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Cyclobutane-thymine dimers (CTDs), the most common DNA lesion induced by UV radiation, cause 30°bending and 9°unwinding of the DNA helix. We prepared site-specific CTDs within a short sequence bracketed by strong nucleosome-positioning sequences. The rotational setting of CTDs over one turn of the helix near the dyad center on the histone surface was analyzed by hydroxyl radical footprinting. Surprisingly, the position of CTDs over one turn of the helix does not affect the rotational setting of DNA on the nucleosome surface. Gel-shift analysis indicates that one CTD destabilizes histone-DNA interactions by 0.6 or 1.1 kJ/mol when facing away or toward the histone surface, respectively. Thus, 0.5 kJ/mol energy penalty for a buried CTD is not enough to change the rotational setting of sequences with strong rotational preference. The effect of rotational setting on CTD removal by nucleotide excision repair (NER) was examined using Xenopus oocyte nuclear extracts. The NER rates are only 2-3 times lower in nucleosomes and change by only 1.5-fold when CTDs face away or toward the histone surface. Therefore, in Xenopus nuclear extracts, the rotational orientation of CTDs on nucleosomes has surprisingly little effect on rates of repair. These results indicate that nucleosome dynamics and/or chromatin remodeling may facilitate NER in gaining access to DNA damage in nucleosomes.In eukaryotes, DNA is organized in chromatin structures within the cell nucleus. The chromatin serves a dual purpose, tight DNA packing within the nucleus and organization of dynamic processes such as DNA transcription, replication, and repair. Of these, DNA repair protects genomic integrity from DNA-damaging agents and is vital for cell survival (1). Indeed, occasional failures in DNA repair can lead to aging and to multiple diseases, including cancer (2, 3). When DNA is irradiated with UV light, adjacent pyrimidines can form stable covalent bonds, yielding cis-syn cyclobutane-pyrimidine dimers (CPDs).5 A common UV lesion caused by exposure to direct sunlight, CPDs can lead to skin cancer, one of the most common forms of cancer (4). The CPD lesion can stall DNA replication (5) and transcription (6) and disrupt DNA interactions with other proteins that regulate gene expression (6). Each of these events can lead to genetic instability.The effect of chromatin structure on repair of UV damage was first implicated by the findings of Wilkins and Hart (7). These authors showed that UV-induced lesions in permeable human cells are removed more slowly from DNA that is less accessible to lesion-specific nucleases in chromatin. It was then found that newly repaired DNA in UVirradiated human fibroblasts is initially more accessible to exogenous nucleases than bulk DNA in chromatin (8) and that nucleosome rearrangement occurs in these regions (9). Studies with a yeast mini-chromosome showed that repair of CPDs is faster in nucleosome-free segments of DNA, being highest in the transcribed strand of a selectable gene and correlating with transcription rate in diff...

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The structure of d(CGCGAAT[ ]TCGCG)-d(CGCGAATTCGCG): the incorporation of a thymine photodimer into a B-DNA helix

Cited by 74 publications

References 16 publications

Spermine-DNA interactions: a theoretical study.

Spermine-DNA interactions: a theoretical study.

NMR studies of bipyrimidine cyclobutane photodimers

Accommodation and Repair of a UV Photoproduct in DNA at Different Rotational Settings on the Nucleosome Surface

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