Flexibility and Curvature of Duplex DNA Containing Mismatched Sites as a Function of Temperature

Marathias, Vasilios M.; Jerkovic, Bozidar; Arthanari, Haribabu; Bolton, Philip H.

doi:10.1021/bi9916630

Cited by 16 publications

(27 citation statements)

References 46 publications

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“…[31] Second, mismatched dsDNA has greater flexibility than fully matched dsDNA; the mismatched base pair can significantly increase the local flexibility of dsDNA by acting as a localized flexible joint. [32] Third, previous reports show that Ag ions could selectively bind to the cytosinecytosine mismatched base pair, as well as chemically modified uracil pairs in dsDNA, and Ag ions have higher affinity for denatured dsDNA than natural dsDNA. [33][34][35][36] On the basis of these findings, a possible formation mechanism is proposed.…”

Section: Resultsmentioning

confidence: 98%

Site‐Specific DNA‐Programmed Growth of Fluorescent and Functional Silver Nanoclusters

Huang

et al. 2011

Chemistry A European J

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Precise organization of metallic nanoclusters on DNA scaffolds holds great interest for nanopatterned materials that may find uses in electronics, sensors, medicine, and many other fields. Herein, we report the site-specific growth of fluorescent silver nanoclusters by using a mismatched double-stranded DNA template. Few-atom, molecular-scale Ag clusters are found to localize at the mismatched site and the metallized DNA retains its integrity. The DNA-encapsulated nanoclusters can be utilized as functional biological probes to identify single-nucleotide polymorphisms by taking advantage of the very bright fluorescence and excellent photostability of the nanoclusters. This approach offers the possibility of constructing novel DNA-based nanomaterials and nanomechanical devices with more sophisticated functions and will be highly beneficial in future biochemical, pharmaceutical, nanomechanical, and electronic applications.

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Section: Resultsmentioning

confidence: 98%

Site‐Specific DNA‐Programmed Growth of Fluorescent and Functional Silver Nanoclusters

Huang

et al. 2011

Chemistry A European J

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“…Given the critical role of base pair flipping in glycosylase mechanisms, we chose to focus on changes in spontaneous base pair opening dynamics around the 8oxoG lesion. However, the bending, curvature, or dynamic movement of 8oxoG-containing DNA on other time scales or other size scales may yet prove to be more distinctive than the base pair opening dynamics (16, 62). …”

Section: Discussionmentioning

confidence: 99%

Hidden in Plain Sight: Subtle Effects of the 8-Oxoguanine Lesion on the Structure, Dynamics, and Thermodynamics of a 15-Base Pair Oligodeoxynucleotide Duplex

et al. 2011

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The base lesion 8-oxoguanine is formed readily by oxidation of DNA, potentially leading to G→T transversion mutations. Despite the apparent similarity of 8-oxoguanine-cytosine base pairs to normal guanine-cytosine base pairs, cellular base excision repair systems effectively recognize the lesion base. Here we apply several techniques to examine a single 8-oxoguanine lesion at the center of a nonpalindromic 15-mer duplex oligonucleotide in an effort to determine what, if anything, distinguishes an 8-oxoguanine-cytosine base pair from a normal base pair. The lesion duplex is globally almost indistinguishable from the unmodified parent duplex using CD spectroscopy and UV melting thermodynamics. The DNA mismatch-detecting photocleavage agent Rh(bpy)2chrysi3+ cleaves only weakly and nonspecifically, revealing that the 8oxoG-C pair is locally stable at the level of the individual base pairs. NMR spectra are also consistent with a well-conserved B-form duplex structure. In the 2D NOESY spectra, base-sugar and imino-imino crosspeaks are strikingly similar between parent and lesion duplexes. Changes in chemical shift due to the 8oxoG lesion are localized to its complementary cytosine and to the 2–3 base pairs immediately flanking the lesion on the lesion strand. Residues further removed from the lesion are shown to be unperturbed by its presence. Notably, imino exchange experiments indicate that the 8-oxoguanine-cytosine pair is strong and stable, with an apparent equilibrium constant for opening equal to that of other internal guanine-cytosine base pairs, on the order of 10−6. This collection of experiments shows that the 8-oxoguanine-cytosine base pair is incredibly stable and similar to the native pair.

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“…The structural effects of increasing the size of a mismatched region are not well understood. However, mismatches do confer helix flexibility, and a substrate with a 3-bp bubble is more flexible than one containing a single bp mismatch (36,37).…”

Section: Ddb Recognizes Helical Distortion Rather Than Specific Dna Lmentioning

confidence: 99%

DDB1-DDB2 (Xeroderma Pigmentosum Group E) Protein Complex Recognizes a Cyclobutane Pyrimidine Dimer, Mismatches, Apurinic/Apyrimidinic Sites, and Compound Lesions in DNA

Wittschieben

Iwai

Wood

2005

Journal of Biological Chemistry

144

122

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The DDB protein complex, comprising the subunits DDB1 and DDB2, binds tightly to UV light-irradiated DNA. Mutations in DDB2 are responsible for xeroderma pigmentosum group E, a disorder with defects in nucleotide excision repair of DNA. Both subunits are also components of a complex involved in ubiquitin-mediated proteolysis. Cellular defects in DDB2 disable repair of the major UV radiation photoproduct in DNA, a cyclobutane pyrimidine dimer, but no significant direct binding of DDB to this photoproduct in DNA has ever been demonstrated. Thus, it has been uncertain how DDB could play a specific role in DNA repair of such damage. We investigated DDB function using highly purified proteins. Co-purified DDB1-DDB2 or DDB reconstituted with individual DDB1 and DDB2 subunits binds to damaged DNA as a ternary complex. We found that DDB can indeed recognize a cyclobutane pyrimidine dimer in DNA with an affinity (K a app ) 6-fold higher than that of nondamaged DNA. The DDB1-DDB2 complex also bound with high specificity to a UV radiation-induced (6-4) photoproduct and to an apurinic site in DNA. Unexpectedly, DDB also bound avidly to DNA containing a 2-or 3-bp mismatch (and does not bind well to DNA containing larger mismatches). These data indicate that DDB does not detect lesions per se. It instead recognizes other structural features of damaged DNA, acting as a sensor that probes DNA for a subset of conformational changes. Lesions recognized may include those arising when translesion polymerases such as POLH incorporate bases across from DNA lesions caused by UV radiation.The human disorder xeroderma pigmentosum (XP) 2 has been intensely studied because of the striking phenotypes of sunlight sensitivity, predisposition to skin cancer, and an association with defects in DNA repair. Seven of the eight complementation groups of the disorder (designated XP-A through XP-G) have defects in nucleotide excision repair (NER) of damaged DNA (1). An eighth group, XP-V, is defective in DNA POLH (pol ) (2), which can bypass the major photoproduct caused by UV radiation in DNA, the cis-syn cyclobutane pyrimidine dimer (CPD). The clinical and cellular characteristics of XP group E are similar to those of the other XP complementation groups but are generally milder. The overall level of NER as measured by unscheduled DNA synthesis in XP-E cells is 50 -80% of normal cells. The gene defective in the XP-E group is DDB2. The 48-kDa DDB2 protein, together with the 127-kDa DDB1 protein (3-5), constitute the DNA damage binding factor known as DDB or UV-DDB (6). The DDB subunits are also found in a protein complex that includes components of a cullinbased ubiquitin ligase as well as the COP9 signalosome (7). The function and physiological substrates of this complex are presently unclear (8).Despite the ability of the DDB protein to bind UV light-irradiated DNA, the specific role of DDB in NER is uncertain. One difficulty in determining the function is that NER can be reconstituted with purified components and damaged naked DNA in the absence ...

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Flexibility and Curvature of Duplex DNA Containing Mismatched Sites as a Function of Temperature

Cited by 16 publications

References 46 publications

Site‐Specific DNA‐Programmed Growth of Fluorescent and Functional Silver Nanoclusters

Site‐Specific DNA‐Programmed Growth of Fluorescent and Functional Silver Nanoclusters

Hidden in Plain Sight: Subtle Effects of the 8-Oxoguanine Lesion on the Structure, Dynamics, and Thermodynamics of a 15-Base Pair Oligodeoxynucleotide Duplex

DDB1-DDB2 (Xeroderma Pigmentosum Group E) Protein Complex Recognizes a Cyclobutane Pyrimidine Dimer, Mismatches, Apurinic/Apyrimidinic Sites, and Compound Lesions in DNA

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