Design, synthesis, and characterization of nucleosomes containing site-specific DNA damage

Taylor, John‐Stephen

doi:10.1016/j.dnarep.2015.09.025

Cited by 13 publications

(12 citation statements)

References 83 publications

(130 reference statements)

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“…see ]. These studies helped form the basis for our understanding of the “efficiency” of DNA excision repair [both nucleotide excision repair (NER) and base excision repair (BER)] in chromatin . Early on, it was clear that some classes of DNA lesions ( e.g .…”

Section: Uv Damage To Dna In Chromatin (Pre‐genomic Era)mentioning

confidence: 99%

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UV‐Induced DNA Damage and Mutagenesis in Chromatin

Mao

Wyrick

Roberts

et al. 2016

Photochem & Photobiology

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UV radiation induces photolesions that distort the DNA double helix and, if not repaired, can cause severe biological consequences, including mutagenesis or cell death. In eukaryotes, both the formation and repair of UV damage occur in the context of chromatin, in which genomic DNA is packaged with histones into nucleosomes and higher-order chromatin structures. Here, we review how chromatin impacts the formation of UV photoproducts in eukaryotic cells. We describe the initial discovery that nucleosomes and other DNA-binding proteins induce characteristic ‘photofootprints’ during the formation of UV photoproducts. We also describe recent progress in genome-wide methods for mapping UV damage, which echoes early biochemical studies, and highlights the role of nucleosomes and transcription factors in UV damage formation and repair at unprecedented resolution. Finally, we discuss our current understanding of how the distribution and repair of UV-induced DNA damage influence mutagenesis in human skin cancers.

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Section: Uv Damage To Dna In Chromatin (Pre‐genomic Era)mentioning

confidence: 99%

“…Although these studies are beyond the scope of the present review, the reader is referred to recent reviews that cover these topics [ e.g . ].…”

Section: Uv Damage To Dna In Chromatin (Pre‐genomic Era)mentioning

confidence: 99%

UV‐Induced DNA Damage and Mutagenesis in Chromatin

Mao

Wyrick

Roberts

et al. 2016

Photochem & Photobiology

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“…Most of DNA deformations take place in the SHL ± 1.5 zone. It has an 298 increased binding of DNA proteins and it is most susceptible to DNA damage [38].…”

Section: Patterns In Yeastmentioning

confidence: 99%

“…In addition to the 34 sequence composition there are other factors in vivo such as post-translational 35 modifications (PTM) of histone tails, transcription factor binding and remodeling 36 complexes that influence positioning of nucleosomes and in turn tune chromatin 37 accessibility and gene expression [5,18]. 38 It was shown that nucleosome remodeling takes place in response to stress and alters 39 a gene expression. A single cell study performed on nucleosomes in yeast under glucose 40 rich (PHO5 gene is silenced) and glucose starvation (PHO5 gene is expressed) 41 conditions revealed that under starvation yeast cells lose nucleosomes in the PHO5 42 promoter [2].…”

Section: Introductionmentioning

confidence: 99%

Nucleosome positioning sequence patterns as packing or regulatory

Pranckevičienė

Hosid

Liang

et al. 2019

Preprint

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Nucleosome positioning DNA sequence patterns (NPS) -usually distributions of particular dinucleotides or other sequence elements in nucleosomal DNA -at least partially determine chromatin structure and arrangements of nucleosomes that in turn affect gene expression. Statistically, NPS are defined as oscillations of the dinucleotide periodicity with about 10 base pairs (bp) which reflects the double helix period. We compared the nucleosomal DNA patterns in mouse, human and yeast organisms and observed few distinctive patterns that can be termed as packing and regulatory referring to distinctive modes of chromatin function. For the first time the NPS patterns in nucleus accumbens cells (NAC) in mouse brain were characterized and compared to the patterns in human CD4+ and apoptotic lymphocyte cells and well studied patterns in August 28, 2019 1/23 yeast. The NPS patterns in human CD4+ cells and mouse brain cells had very high positive correlation. However, there was no correlation between them and patterns in human apoptotic lymphocyte cells and yeast, but the latter two were highly correlated with each other. By their dinucleotide arrangements the analyzed NPS patterns classified into stable canonical WW/SS (W=A or T and S=C or G dinucleotide) and less stable RR/YY (R=A or G and Y =C or T dinucleotide) patterns and anti-patterns.In the anti-patterns positioning of the dinucleotides is flipped compared to those in the regular patterns. Stable canonical WW/SS patterns and anti-patterns are ubiquitously observed in many organisms and they had high resemblance between yeast and human apoptotic cells. Less stable RR/YY patterns had higher positive correlation between mouse and normal human cells. Our analysis and evidence from scientific literature lead to idea that various distinct patterns in nucleosomal DNA can be related to the two roles of the chromatin: packing (WW/SS) and regulatory (RR/YY and "anti"). Author summaryPrecise positioning of nucleosomes on DNA sequence is essential for gene regulatory processes. Two main classes of nucleosome positioning sequence (NPS) patterns with a periodicity of 10bp for their sequence elements were previously described. In the 1st class AA,TT and other WW dinucleotides (W= A or T) tend to occur together in the major groove of DNA closest to the histone octamer, while SS dinucleotides (S= G or C) are primarily positioned in the major groove facing outward. In the 2nd class AA and TT are structurally separated (AA backbone near the histone octamer, and TT backbone further away), but grouped with other RR (R is purine A or G) and YY (Y is pyrimidine C or T) dinucleotides. In [8] we also described novel anti-NPS patterns, inverse to the conventional NPS patterns: WW runs inverse to SS, RR inverse to YY.We demonstrated that Yeast nucleosomes in promoters show higher correlation to the RR/YY pattern whereas novel anti-NPS patterns are viable for nucleosomes in the promoters of stress associated genes related to active chromatin remodeling. In the present study we attribute different ...

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“…23 Herein, the inuence of the vicinal presence of an abasic site near an 8-oxodG lesion and Tg:G mismatch was evaluated by estimating the cleavage efficiency of the repair specic enzymes hOGG1 and hNTH1, respectively, in a two lesion, as well as a three lesion, oligonucleotide model. Our studies show that the abasic site presents a signicant hurdle in the efficient repair of the Tg:G mismatch and 8-oxodG lesion by introducing conformational destabilization in the DNA that prevents proper interaction of the lesion specic enzymes with the lesions.…”

Section: 22mentioning

confidence: 99%

Vicinal abasic site impaired processing of a Tg:G mismatch and 8-oxoguanine lesions in three-component bistranded clustered DNA damage

et al. 2018

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The occurrence of 7,8-dihydro-8-oxo-2 0 deoxyguanosine (8-oxodG), thymine glycol:guanine (Tg:G) mismatch and abasic site DNA damage lesions in close proximity induce repair refractive multicomponent clustered DNA damage. Herein, the influence of abasic sites in the processing of 8-oxodG lesion and Tg:G mismatch bistranded cluster is evaluated. Abasic sites are found to impart conformational destabilization that appreciably hinders the repair activity of the other lesions whenever present in a cluster combination. The repair process reduces the formation of double strand breaks (DSBs) and renders this three-lesion combination a non-DSB forming cluster. The stability of the DNA duplex harbouring these three lesions is highly compromised due to altered base helicity and base stacking phenomena leading to impaired repair.Damaged lesions in deoxyribonucleic acid (DNA) are ubiquitous due to the exposure of cells to various exogenous sources, including ionizing radiation and toxins, as well as endogenous metabolism. 1,2 5-Methyl cytosine (5-mC) residues in DNA are vulnerable to radiation-induced oxidation that could generate a Tg:G mismatch.3 In addition, stripping of purine or pyrimidine bases giving rise to potentially mutagenic abasic sites is a familiar event.4 8-oxodG is one of the most common DNA damage lesions that plays a critical role in mutagenesis and carcinogenesis.5 However, the present understanding of the repair pattern of three-component multilesion clustered DNA damage is very limited, particularly in clusters containing a Tg:G mismatch and 8-oxodG in the vicinity of abasic sites. Herein, for the rst time, we demonstrate the role of abasic sites in the repair of a Tg:G mismatch and 8-oxodG present in a three component bistranded cluster environment.The DNA repair machinery in our cells has the huge responsibility of repairing chemically unrelated lesions in order to ensure the smooth functioning of cellular processes and maintain genomic integrity.6 Evidently, the challenge for the DNA repair machinery is even greater when multiple lesions are present in close proximity to one another giving rise to multicomponent clustered DNA damage, oen reported as a major outcome of exposure to ionizing radiation.7-12 Subsequent repair takes place through the intervention of various well recruited enzymes of the base excision repair (BER) pathway. 13Specically, in human cells, the repair of abasic sites, 8-oxodG and Tg lesions involves apurinic/apyrimidic endonuclease (APE1), oxoguanine glycosylase (hOGG1) and hNTH1 enzymes, respectively, in the initial stages following the BER pathway. 14,15The attempted repair of bistranded clusters oen leads to the generation of potentially lethal double strand breaks (DSBs) that could lead to deletions, translocations, and fusions. 16Reportedly, bistranded clustered abasic sites are processed to yield DSBs in E. coli leading to cytotoxicity.17 In contrast, most clustered damage systems adopt a hierarchal repair strategy to lessen the DSB formation while attempting repair.18...

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Design, synthesis, and characterization of nucleosomes containing site-specific DNA damage

Cited by 13 publications

References 83 publications

UV‐Induced DNA Damage and Mutagenesis in Chromatin

UV‐Induced DNA Damage and Mutagenesis in Chromatin

Nucleosome positioning sequence patterns as packing or regulatory

Vicinal abasic site impaired processing of a Tg:G mismatch and 8-oxoguanine lesions in three-component bistranded clustered DNA damage

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