Phosphodiesterases Involved in DNA Repair

Weiss, Bernard; Grossman, Lawrence I.

doi:10.1002/9780470123065.ch1

Cited by 51 publications

(14 citation statements)

References 127 publications

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“…The abasic site analog tetrahydrofuran (TF) has been used in most studies as a substitute for abasic sites since it was first employed [24], as it can be easily incorporated into oligonucleotide substrates as a nucleoside analog and is thermally and chemically more stable than the biologically-relevant, glycosylase generated 2′-deoxyribose AP sites (See figure 1A for structures of the two abasic sites) [25]. The TF is a stable ring structure, whereas the AP site is actually an equilibrium mixture of tautomers consisting primarily of α and β anomers of deoxyribofuranose and a low level of the partially hydrated (open chain) form (which themselves are readily subject to a β-elimination reaction leading to single strand breaks in the DNA) [25].…”

Section: Introductionmentioning

confidence: 99%

“…The TF is a stable ring structure, whereas the AP site is actually an equilibrium mixture of tautomers consisting primarily of α and β anomers of deoxyribofuranose and a low level of the partially hydrated (open chain) form (which themselves are readily subject to a β-elimination reaction leading to single strand breaks in the DNA) [25]. Thus, in solution, the two abasic lesions are dynamically different, and it is unclear whether the TF analog acts as a relevant substitute in conditions where the bending of the DNA (due to association with the histones) plays a key role in interaction with its enzyme.…”

Section: Introductionmentioning

confidence: 99%

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Impact of abasic site orientation within nucleosomes on human APE1 endonuclease activity

Hinz

2014

Mutation Research/Fundamental and Molecular Mechanisms of Mutag

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Glycosylases responsible for recognizing DNA lesions and initiating Base Excision Repair (BER) are impeded by the presence of histones, which are essential for compaction of the genetic material in the nucleus. Abasic sites are an abundant mutagenic lesion in the DNA, arising spontaneously and as the product of glycosylase activity, making it a common intermediate in BER. The apurinic/apyrimidinic endonuclease 1 (APE1) recognizes abasic sites and cleaves the DNA backbone adjacent to the lesion, creating the single-strand break essential for the subsequent steps of BER. In this study the endonuclease activity of human APE1 was measured on reconstituted nucleosome core particles (NCPs) with DNA containing enzymatically-created abasic sites (AP) or the abasic site analog tetrahydrofuran (TF) at different rotational positions relative to the histone core surface. The presence of histones on the DNA reduced APE1 activity overall, and the magnitude was greatly influenced by differences in orientation of the lesions along the DNA gyre relative to the histone core. Abasic moieties oriented with their phosphate backbones adjacent to the underlying histones (In) were cleaved less efficiently than those oriented away from the histone core (Out) or between the In and Out orientations (Mid). The impact on APE1 at each orientation was very similar between the AP and TF lesions, highlighting the dependability of the TF abasic analog in APE1 activity measurements in nucleosomes. Measurement of APE1 binding to the NCP substrates reveals a substantial reduction in its interaction with nucleosomes compared to naked DNA, also in a lesion orientation-dependent manner, reinforcing the concept that reduction in APE1 activity on nucleosomes is due to occlusion from its abasic DNA substrate by the histones. These results suggest that APE1 activity in nucleosomes, like BER glycosylases, is primarily regulated by its chance interactions with transiently exposed lesions.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Impact of abasic site orientation within nucleosomes on human APE1 endonuclease activity

Hinz

2014

Mutation Research/Fundamental and Molecular Mechanisms of Mutag

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“…The AP, in which one base is missing and its counterpart in the opposite duplex DNA strand unpaired, cause change of the structural and dynamic properties of DNA that affect the recognition and misreading of lesions by the cellular machinery involved in DNA repair and replication. The presence of these lesions has been shown to slow down, but not block RNA polymerases, virus reverse transcriptase [3] and to cause mis-incorporation of nucleoside triphosphates by a DNA polymerase during replication [4,5]. Thus, the changes in nucleotide sequences of DNA, when replicated and transmitted to future cell generations, become the source of permanent mutations.…”

Section: Introductionmentioning

confidence: 99%

Detection of Abasic Sites in DNA by Electrochemical, Immunoelectrochemical and Acoustic Methods Using OsO₄, 2,2′‐bipyridine as a Probe for Unpaired Thymine Residues

Bartošík¹,

Gajdoš²,

Kostečka³

et al. 2009

Electroanalysis

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We report on comparative analysis of the detection of DNA damage modeled by presence of abasic sites (AP) at defined positions using the chemical modification of the DNA by the complex of osmium tetroxide-2,2-bipyridine (Os, bipy) that selectively binds to unpaired thymine residues in the damaged DNA. AP were detected by electrochemical detection (EC) of the Os, bipy-thymine adducts, by immunoelectrochemical (IE) and by thickness shear mode acoustic methods (TSM). EC method of detection can perfectly distinguish between the number of AP. IE and TSM methods were of comparable sensitivity.

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“…They can arise in DNA as a result of spontaneous hydrolysis of the N-glycosidic bond [1,2] or the removal of altered bases by DNA glycosylases [1,3]. Depurination is likely the most frequent spontaneous alteration that occurs in DNA under physiological conditions [4].…”

Section: Introductionmentioning

confidence: 99%

“…The glycosylases leave a DNA strand containing the sites of base loss and an intact phosphodiester backbone. These lesions are subject to relatively facile b-elimination reaction, which leads to unprocessed DNA strand breaks [3,5,6]. Thus, the AP sites are the main intermediates in chemical mutagenesis [1,7] and DNA damage repair process [1,4,8,9].…”

Section: Introductionmentioning

confidence: 99%

Electrochemical Detection of Abasic Site‐Containing DNA

Dolinnaya¹,

Jan²,

Kawde³

et al. 2006

Electroanalysis

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A simple and rapid approach for detecting apurinic (AP) sites in DNA, based on direct stripping chronopotentiometric measurements of the adenine and guanine nucleobases at a graphite electrode is described. Tetrahydrofuranyl residues, lacking a nucleobase moiety, were utilized for designing the AP sites and were incorporated in 19-mer oligonucleotides. The change of adenine-to-guanine response ratio (A/G) in one-, two-or three-substituted adenosine residues for stable analogs of AP sites was exploited for electrochemical measurements of the adenine loss. The resulting A/G response ratio decreases linearly upon increasing the number of AP sites in the oligonucleotides; the values of A/G electrochemical signals were slightly enhanced when compared to the actual purine content. HPLC analysis of the released nucleobases confirmed that the sulfuric acid-induced oligonucleotide cleavage provides complete apurination and dissolution of the released nucleobases in aqueous solution. Additional experiments with mixtures of free nucleobases and purine nucleosides reveal that the larger A/G ratio observed in the electrochemical analysis of AP-site-containing oligomers is attributed to the influence of the acid and/or thermal decomposition products (particularly the sugar fragments). This study represents the first step in developing a simple and direct electrochemical assay of AP sites in single-stranded DNA.

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Phosphodiesterases Involved in DNA Repair

Cited by 51 publications

References 127 publications

Impact of abasic site orientation within nucleosomes on human APE1 endonuclease activity

Impact of abasic site orientation within nucleosomes on human APE1 endonuclease activity

Detection of Abasic Sites in DNA by Electrochemical, Immunoelectrochemical and Acoustic Methods Using OsO₄, 2,2′‐bipyridine as a Probe for Unpaired Thymine Residues

Electrochemical Detection of Abasic Site‐Containing DNA

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Phosphodiesterases Involved in DNA Repair

Cited by 51 publications

References 127 publications

Impact of abasic site orientation within nucleosomes on human APE1 endonuclease activity

Impact of abasic site orientation within nucleosomes on human APE1 endonuclease activity

Detection of Abasic Sites in DNA by Electrochemical, Immunoelectrochemical and Acoustic Methods Using OsO4, 2,2′‐bipyridine as a Probe for Unpaired Thymine Residues

Electrochemical Detection of Abasic Site‐Containing DNA

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Detection of Abasic Sites in DNA by Electrochemical, Immunoelectrochemical and Acoustic Methods Using OsO₄, 2,2′‐bipyridine as a Probe for Unpaired Thymine Residues