Thermodynamic and base-pairing studies of matched and mismatched DNA dodecamer duplexes containing cis-syn, (6-4) and Dewar photoproducts of TT

Jing, Y.; Kao, Jeff; Taylor, John‐Stephen

doi:10.1093/nar/26.16.3845

Cited by 70 publications

(80 citation statements)

References 60 publications

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“…An NMR study of a duplex DNA with (6 -4)PP revealed that TT-(6 -4)PP greatly distorts the DNA structure and prevents base-pairing with A in the complementary strand (41). However, a mismatched base pair between the 3Ј-T of TT-(6 -4)PP and G forms hydrogen bonds and stabilizes the helix (42,43). Furthermore, the G/T mispair at the 3Ј-T of TT (6 -4)PP retains the normal WatsonCrick-type base-pairing between the 5Ј-T of the TT-(6 -4)PP and an opposed A, and the resultant GA/TT-(6 -4)PP duplex can assume the typical B-form-DNA conformation (44).…”

Section: Discussionmentioning

confidence: 99%

Mutagenic and Nonmutagenic Bypass of DNA Lesions byDrosophila DNA Polymerases dpolη and dpolι

Ishikawa

Uematsu

Mizukoshi

et al. 2001

Journal of Biological Chemistry

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cDNA sequences were identified and isolated that encode Drosophila homologues of human Rad30A and Rad30B called drad30A and drad30B. Here we show that the C-terminal-truncated forms of the drad30A and drad30B gene products, designated dpol⌬C and dpol⌬C, respectively, exhibit DNA polymerase activity. dpol⌬C and dpol⌬C efficiently bypass a cis-syn-cyclobutane thymine-thymine (TT) dimer in a mostly error-free manner. dpol⌬C shows limited ability to bypass a 6 -4-photoproduct ((6 -4)PP) at thymine-thymine (TT-(6 -4)PP) or at thymine-cytosine (TC-(6 -4)PP) in an error-prone manner. dpol⌬C scarcely bypasses these lesions. Thus, the fidelity of translesion synthesis depends on the identity of the lesion and on the polymerase. The human XPV gene product, hpol, bypasses cis-syn-cyclobutane thymine-thymine dimer efficiently in a mostly error-free manner but does not bypass TT-(6 -4)PP, whereas Escherichia coli DNA polymerase V (UmuD 2 C complex) bypasses both lesions, especially TT-(6 -4)PP, in an error-prone manner (Tang, M., Pham, P., Shen, X., Taylor, J. S., O'Donnell, M., Woodgate, R., and Goodman, M. F. (2000) Nature 404, 1014 -1018). Both dpol⌬C and DNA polymerase V preferentially incorporate GA opposite TT-(6 -4)PP. The chemical structure of the lesions and the similarity in the nucleotides incorporated suggest that structural information in the altered bases contribute to nucleotide selection during incorporation opposite these lesions by these polymerases.DNA is frequently damaged by environmental and endogenous genotoxic agents. Although various mechanisms exist to ensure that the majority of DNA damage is recognized and repaired and the integrity of the DNA is faithfully restored, some DNA lesions escape repair and persist in the cell. Unrepaired DNA lesions can block the progress of the replication machinery. To help resolve this problem, cells have specialized polymerases that carry out translesion DNA synthesis (TLS) 1 , which is a mechanism that permits nucleotides to be incorporated opposite lesions. After TLS bypasses the DNA damage, replication can continue with the normal replication machinery downstream of the site of the damage.Recently, a new family of DNA polymerases was identified called the UmuC/DinB/Rev1/Rad30 superfamily (1-3). Several of these polymerases participate in TLS (4 -11), and members of this protein family exhibit lower fidelity and processivity than replicative DNA polymerases (10, 12-15). The lower fidelity enables these polymerases to carry out TLS and the lower processivity facilitates dissociation of these enzymes after bypass of a lesion; this is important because it allows the normal replication machinery, with high fidelity and processivity, to preferentially carry out DNA synthesis distal to the lesion. However, TLS is mutagenic when the base inserted opposite the DNA lesion is different than the base normally inserted opposite an undamaged base at that site. The chemical structure of the lesion is an important determinant for mutagenic or nonmutagenic bypass during TLS. Irr...

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Section: Discussionmentioning

confidence: 99%

Mutagenic and Nonmutagenic Bypass of DNA Lesions byDrosophila DNA Polymerases dpolη and dpolι

Ishikawa

Uematsu

Mizukoshi

et al. 2001

Journal of Biological Chemistry

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“…This discrimination function, presumably mediated by the presence of abnormal hydrophobic attractions on the helical surface and without specificity for a particular type of lesion, allows recognition of all damaged sites that destabilize (including for example cyclobutane pyrimidine dimers; ref. 39) or disrupt Watson-Crick hydrogen bonds. Therefore, XPA protein (together with RPA) may use this versatile strategy to target the human NER system to a wide range of chemically diverse forms of DNA damage.…”

Section: Discussionmentioning

confidence: 99%

Recognition of nonhybridizing base pairs during nucleotide excision repair of DNA

Buschta-Hedayat

Buterin

Heß

et al. 1999

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

103

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Nondistorting C4 backbone adducts serve as molecular tools to analyze the strategy by which a limited number of human nucleotide excision repair (NER) factors recognize an infinite variety of DNA lesions. We have constructed composite DNA substrates containing a noncomplementary site adjacent to a nondistorting C4 adduct to show that the loss of hydrogen bonding contacts between partner strands is an essential signal for the recruitment of NER enzymes. This specific conformational requirement for excision is mediated by the affinity of xeroderma pigmentosum group A (XPA) protein for nonhybridizing sites in duplex DNA. XPA recognizes defective Watson-Crick base pair conformations even in the absence of DNA adducts or other covalent modifications, apparently through detection of hydrophobic base components that are abnormally exposed to the double helical surface. This recognition function of XPA is enhanced by replication protein A (RPA) such that, in combination, XPA and RPA constitute a potent molecular sensor of denatured base pairs. Our results indicate that the XPA-RPA complex may promote damage recognition by monitoring Watson-Crick base pair integrity, thereby recruiting the human NER system preferentially to sites where hybridization between complementary strands is weakened or entirely disrupted.

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“…Given that little difference has been observed in excision repair rates between inside and outside TT CPDs (41), the large difference in deamination rates could explain, at least in part, the origin of UV mutation hotspots and coldspots in phased nucleosomes that would arise following polymerase bypass. On the other hand, deamination of an m C-containing CPD will result in a T⅐G mismatch, which has been shown to destabilize the DNA duplex by 0.7 kcal/mol (54). This duplex destabilization may further destabilize the nucleosome, which has already been shown to be destabilized by 0.14 -0.24 kcal/mol by a TT CPD (41), and facilitate recognition by histone modification and/or excision repair systems.…”

Section: Figurementioning

confidence: 99%

Rotational Position of a 5-Methylcytosine-containing Cyclobutane Pyrimidine Dimer in a Nucleosome Greatly Affects Its Deamination Rate

Song

Cannistraro

Taylor

2011

Journal of Biological Chemistry

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C to T mutation hotspots in skin cancers occur primarily at methylated CpG sites that coincide with sites of UV-induced cyclobutane pyrimidine dimer (CPD) formation. These mutations are proposed to arise from the insertion of A by DNA polymerase opposite the T that results from deamination of the methylC ( m C) within the CPD. Although the frequency of CPD formation and repair is modestly modulated by its rotational position within a nucleosome, the effect of position on the rate of m C deamination in a CPD has not been previously studied. We now report that deamination of a T m C CPD whose sugar phosphate backbone is positioned against the histone core surface decreases by a factor of 4.7, whereas that of a T m C CPD positioned away from the surface increases by a factor of 8.9 when compared with unbound DNA. Because the m Cs undergoing deamination are in similar steric environments, the difference in rate appears to be a consequence of a difference in the flexibility and compression of the two sites due to DNA bending. Considering that formation of the CPD positioned away from the surface is also enhanced by a factor of two, a T m CG site in this position might be expected to have up to an 84-fold higher probability of resulting in a UV-induced m C to T mutation than one positioned against the surface. These results indicate that rotational position may play an important role in the formation of UV-induced C to T mutation hotspots, as well as in the mutagenic mechanism of other DNA lesions.

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Thermodynamic and base-pairing studies of matched and mismatched DNA dodecamer duplexes containing cis-syn, (6-4) and Dewar photoproducts of TT

Cited by 70 publications

References 60 publications

Mutagenic and Nonmutagenic Bypass of DNA Lesions byDrosophila DNA Polymerases dpolη and dpolι

Mutagenic and Nonmutagenic Bypass of DNA Lesions byDrosophila DNA Polymerases dpolη and dpolι

Recognition of nonhybridizing base pairs during nucleotide excision repair of DNA

Rotational Position of a 5-Methylcytosine-containing Cyclobutane Pyrimidine Dimer in a Nucleosome Greatly Affects Its Deamination Rate

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