Differences in the Access of Lesions to the Nucleotide Excision Repair Machinery in Nucleosomes

Cai, Yuqin; Kropachev, Konstantin; Terzidis, Michael A.; Masi, Annalisa; Chatgilialoglu, Chryssostomos; Shafirovich, Vladimir; Geacintov, Nicholas E.; Broyde, Suse

doi:10.1021/acs.biochem.5b00564

Cited by 17 publications

(16 citation statements)

References 39 publications

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“…Within the three tertiary forms, the very low levels recorded for purine 5 0 ,8-cyclo-2 0 -deoxynucleoside lesions are in agreement with the low efficiency of such radiation-induced lesions in cellular DNA [11]. On the contrary, these lesions are harmful since they accumulate with aging in a tissue-specific manner (liver > kidney > brain) [33,41] suggesting that DNA repair mechanisms are inadequate to effectively deal with these lesions [16].…”

Section: Quantification Of Purine Lesions In Dsdna Conformersmentioning

confidence: 57%

“…In particular, under physiological levels of oxygen (e.g. recently been studied in nucleosomes along with DNA-histone interactions and local electrostatic potentials, with emphasis on the hydrogen bond between Lys115 of histone H3 and the DNA backbone which has been observed in the case of cdG lesions [16]. Second, given the importance of non-coding repeat guanine-rich Scheme 2.…”

Section: Introductionmentioning

confidence: 99%

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Radical-induced purine lesion formation is dependent on DNA helical topology

Terzidis

Prisecaru

Molphy

et al. 2016

Free Radical Research

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Herein we report the quantification of purine lesions arising from gamma-radiation sourced hydroxyl radicals (HO · ) on tertiary dsDNA helical forms of supercoiled (SC), open circular (OC), and linear (L) conformation, along with single-stranded folded and non-folded sequences of guanine-rich DNA in selected G-quadruplex structures. We identify that DNA helical topology and folding plays major, and unexpected, roles in the formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dG) and 8-oxo-7,8-dihydro-2'-deoxyadenosine (8-oxo-dA), along with tandem-type purine lesions 5 (mutTel24) were exposed to HO · radicals and purine lesions were then quantified via stable isotope dilution LC-MS/MS analysis. Purine oxidation in dsDNA follows L > OC ) SC indicating greater damage towards the extended B-DNA topology. Conversely, G-quadruplex sequences were significantly more resistant toward purine oxidation in their unfolded states as compared with G-tetrad folded topologies; this effect is confirmed upon comparative analysis of Tel22 ($50% solution folded) and mutTel24 ($90% solution folded). In an effort to identify the accessibly of hydroxyl radicals to quadruplex purine nucleobases, G-quadruplex solvent cavities were then modeled at 1.33 Å with evidence suggesting that folded G-tetrads may act as potential oxidant traps to protect against chromosomal DNA damage. ARTICLE HISTORY

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Section: Quantification Of Purine Lesions In Dsdna Conformersmentioning

confidence: 57%

Section: Introductionmentioning

confidence: 99%

Radical-induced purine lesion formation is dependent on DNA helical topology

Terzidis

Prisecaru

Molphy

et al. 2016

Free Radical Research

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“…the 5′R isomer being two times more efficiently repaired by NER than the 5′S isomer [15]. Molecular modeling and dynamics simulation elucidated that the different efficiency of NER is associated with the greater DNA backbone distortion caused by the 5′R isomer compared to the 5′S diastereomer [15,16] of the lesion. It has been found that these lesions are removed with a low efficiency by NER compared to other bulky DNA adducts [14], thereby leading to the accumulation of these oxidative lesions in the genome [1,14].…”

Section: Preprintsmentioning

confidence: 97%

Diastereomeric Recognition of 5',8-cyclo-2'-deoxyadenosine Lesions by Human poly(ADP-ribose) Polymerase 1 in Biomimetic Model

Masi¹,

Sabbia²,

Ferreri³

et al. 2018

Preprint

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Abstract5′,8-Cyclo-2′-deoxyadenosine (cdA), in the 5′R and 5′Sdiastereomeric forms, are typical non strand-break oxidative DNA lesions, induced by hydroxyl radicals, with emerging importance as a molecular marker. These lesions are exclusively repaired by nucleotide excision repair (NER) mechanism with a low efficiency, thus readily accumulating in the genome. Poly(ADP-ribose) polymerase1 (PARP1) acts as an early responder to DNA damage and plays a key role as a nick sensor in the maintenance of the integrity of the genome by recognizing nicked DNA. So far, it was unknown whether the diastereomeric cdA lesions could induce specific PARP1 binding. Here we provide the first evidence of PARP1 to selectively recognize the diastereomeric lesions 5′S-cdA and 5′R-cdA in vitro as compared to deoxyadenosine in model DNA substrates (23-mers) by using circular dichroism,fluorescence spectroscopy, immunoblotting analysis and gel mobility shift assay. Several features of the recognition of the damaged and undamaged oligonucleotides by PARP1were characterized. Remarkably, PARP1 efficiently binds to both cdA lesions in the double stranded (ds)-oligonucleotides. In particular, PARP1 proved to bind 5′S-cdAwith a higher affinity constant for the 5'S lesion in a model of ds DNA than 5′R-cdA, showing different recognition patterns, also compared with undamaged dA. This new finding highlights the ability of PARP1 to recognize and differentiate the distorted DNA backbone in a biomimetic system caused by different diastereomeric forms of a cdA lesion.

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“…Both cdG and cdA lesions, in their 5 0 S and 5 0 R diastereomeric forms, are repaired at low efficiency by the human nucleotide excision repair (NER) pathway, there being ca. 2 times greater efficacy for 5 0 R over 5 0 S diastereomer repair, owing to greater DNA backbone distortions encountered in 5 0 R diastereomeric lesion-containing sequences [47,48]. Given the known correlation among oxidative DNA damage and its repair in trinucleotide repeats (TNR), it was investigated whether TNR instability can be induced by the cdA lesions during replication and repeat [49].…”

Section: Working Group 2: Models Of Dna Damage and Consequencesmentioning

confidence: 99%

COST Action CM1201 “Biomimetic Radical Chemistry”: free radical chemistry successfully meets many disciplines

Ferreri

Golding

Jahn

et al. 2016

Free Radical Research

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The COST Action CM1201 "Biomimetic Radical Chemistry" has been active since December 2012 for 4 years, developing research topics organized into four working groups: WG1 -Radical Enzymes, WG2 -Models of DNA damage and consequences, WG3 -Membrane stress, signalling and defenses, and WG4 -Bio-inspired synthetic strategies. International collaborations have been established among the participating 80 research groups with brilliant interdisciplinary achievements. Free radical research with a biomimetic approach has been realized in the COST Action and are summarized in this overview by the four WG leaders. ARTICLE HISTORY

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Differences in the Access of Lesions to the Nucleotide Excision Repair Machinery in Nucleosomes

Cited by 17 publications

References 39 publications

Radical-induced purine lesion formation is dependent on DNA helical topology

Radical-induced purine lesion formation is dependent on DNA helical topology

Diastereomeric Recognition of 5',8-cyclo-2'-deoxyadenosine Lesions by Human poly(ADP-ribose) Polymerase 1 in Biomimetic Model

COST Action CM1201 “Biomimetic Radical Chemistry”: free radical chemistry successfully meets many disciplines

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