Increased levels of 5′,8-Cyclopurine DNA lesions in inflammatory bowel diseases

Masi, Annalisa; Fortini, Paola; Krokidis, Marios G.; Romeo, Erminia; Bascietto, C.; Angelis, Paola De; Guglielmi, Valeria; Chatgilialoglu, Chryssostomos

doi:10.1016/j.redox.2020.101562

Cited by 20 publications

(12 citation statements)

References 55 publications

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“…There are at least two factors playing a role: (i) the more efficient repair of the 5′ R diastereomers of the cPu reported in human cell extracts by NER [ 40 ], and (ii) the structural characteristics of the transition states associated with the C5′ radical cyclization that generates the cPu lesions [ 29 ]. In our recent work on inflamed IBD-colon biopsies versus their normal counterpart, we found the 5′ S diastereomers of cdA and cdG are at higher levels than their 5′ R counterparts, supporting the more efficient repair of the 5′ R diastereomers of the cPu reported in human cell extracts [ 57 ]. On the other hand, in the present study we measured the 5′ R /5′ S ratio to be identical for wtCSB and defective CSB (being 0.58–0.59 for cdG and 2.82–2.84 for cdA), which is in agreement with the recent published values for EUE-pBD650 (wt) and EUE-siXPA (deficient) human embryonic epithelial cell lines (0.29–0.32 for cdG and 2.69–2.94 for cdA and independent of oxygen tension) [ 60 ].…”

Section: Discussionsupporting

confidence: 70%

“…Under these conditions a wide variety of biomolecules, including nucleic acids, are damaged, but also the activity of the DNA repair machinery is inhibited causing DNA damage accumulation [ 54 , 55 ]. A positive correlation between the increase in the iNOS expression levels and the accumulation of DNA damage has been reported [ 50 , 56 , 57 ]. It is well known that iNOS protein is responsible for the production of cellular nitric oxide (NO • ), which, reacting with superoxide radical anion (O 2 •– ), forms peroxynitrite (ONOO − ) (see Appendix A Figure A2 ) [ 28 ].…”

Section: Discussionmentioning

confidence: 99%

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Oxygen-Dependent Accumulation of Purine DNA Lesions in Cockayne Syndrome Cells

Krokidis

D’Errico

Pascucci

et al. 2020

Cells

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Cockayne Syndrome (CS) is an autosomal recessive neurodegenerative premature aging disorder associated with defects in nucleotide excision repair (NER). Cells from CS patients, with mutations in CSA or CSB genes, present elevated levels of reactive oxygen species (ROS) and are defective in the repair of a variety of oxidatively generated DNA lesions. In this study, six purine lesions were ascertained in wild type (wt) CSA, defective CSA, wtCSB and defective CSB-transformed fibroblasts under different oxygen tensions (hyperoxic 21%, physioxic 5% and hypoxic 1%). In particular, the four 5′,8-cyclopurine (cPu) and the two 8-oxo-purine (8-oxo-Pu) lesions were accurately quantified by LC-MS/MS analysis using isotopomeric internal standards after an enzymatic digestion procedure. cPu levels were found comparable to 8-oxo-Pu in all cases (3–6 lesions/106 nucleotides), slightly increasing on going from hyperoxia to physioxia to hypoxia. Moreover, higher levels of four cPu were observed under hypoxia in both CSA and CSB-defective cells as compared to normal counterparts, along with a significant enhancement of 8-oxo-Pu. These findings revealed that exposure to different oxygen tensions induced oxidative DNA damage in CS cells, repairable by NER or base excision repair (BER) pathways. In NER-defective CS patients, these results support the hypothesis that the clinical neurological features might be connected to the accumulation of cPu. Moreover, the elimination of dysfunctional mitochondria in CS cells is associated with a reduction in the oxidative DNA damage.

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Section: Discussionsupporting

confidence: 70%

Section: Discussionmentioning

confidence: 99%

Oxygen-Dependent Accumulation of Purine DNA Lesions in Cockayne Syndrome Cells

Krokidis

D’Errico

Pascucci

et al. 2020

Cells

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“…Oxidative stress is the result from imbalance between reactive oxygen species (ROS) overproduction and endogenous antioxidants. Excessive ROS triggered multifarious cellular stress response, such as endoplasmic reticulum (ER) stress, inflammatory reaction, genotoxic stress and hypoxia [ [70] , [71] , [72] , [73] ]. A recent plant study found ROS induced the activation of GCN2 kinase in Arabidopsis [ 74 ].…”

Section: Discussionmentioning

confidence: 99%

Melatonin protects against environmental stress-induced fetal growth restriction via suppressing ROS-mediated GCN2/ATF4/BNIP3-dependent mitophagy in placental trophoblasts

Zhu

Shi

et al. 2021

Redox Biology

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“…Knowing the nature, interdependence, and implications of this type of damage is particularly important for its diagnostic potential. CdPus are considered biomarkers of oxidative DNA damage in the case of atherosclerosis, prediabetes, or inflammatory bowel disease [ 32 , 33 , 34 ]. Additionally, understanding the impact of radiation on genetic material is crucial for its new applications in medicine, pharmacy, and food science [ 35 ].…”

Section: Introductionmentioning

confidence: 99%

How (5′S) and (5′R) 5′,8-Cyclo-2′-Deoxypurines Affect Base Excision Repair of Clustered DNA Damage in Nuclear Extracts of xrs5 Cells? A Biochemical Study

Boguszewska

Szewczuk

Kaźmierczak-Barańska

et al. 2021

Cells

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The clustered DNA lesions (CDLs) are a characteristic feature of ionizing radiation’s impact on the human genetic material. CDLs impair the efficiency of cellular repair machinery, especially base excision repair (BER). When CDLs contain a lesion repaired by BER (e.g., apurinic/apyrimidinic (AP) sites) and a bulkier 5′,8-cyclo-2′-deoxypurine (cdPu), which is not a substrate for BER, the repair efficiency of the first one may be affected. The cdPus’ influence on the efficiency of nuclear BER in xrs5 cells have been investigated using synthetic oligonucleotides with bi-stranded CDL (containing (5′S) 5′,8-cyclo-2′-deoxyadenosine (ScdA), (5′R) 5′,8-cyclo-2′-deoxyadenosine (RcdA), (5′S) 5′,8-cyclo-2′-deoxyguanosine (ScdG) or (5′R) 5′,8-cyclo-2′-deoxyguanosine (RcdG) in one strand and an AP site in the other strand at different interlesion distances). Here, for the first time, the impact of ScdG and RcdG was experimentally tested in the context of nuclear BER. This study shows that the presence of RcdA inhibits BER more than ScdA; however, ScdG decreases repair level more than RcdG. Moreover, AP sites located ≤10 base pairs to the cdPu on its 5′-end side were repaired less efficiently than AP sites located ≤10 base pairs on the 3′-end side of cdPu. The strand with an AP site placed opposite cdPu or one base in the 5′-end direction was not reconstituted for cdA nor cdG. CdPus affect the repair of the other lesion within the CDL. It may translate to a prolonged lifetime of unrepaired lesions leading to mutations and impaired cellular processes. Therefore, future research should focus on exploring this subject in more detail.

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Increased levels of 5′,8-Cyclopurine DNA lesions in inflammatory bowel diseases

Cited by 20 publications

References 55 publications

Oxygen-Dependent Accumulation of Purine DNA Lesions in Cockayne Syndrome Cells

Oxygen-Dependent Accumulation of Purine DNA Lesions in Cockayne Syndrome Cells

Melatonin protects against environmental stress-induced fetal growth restriction via suppressing ROS-mediated GCN2/ATF4/BNIP3-dependent mitophagy in placental trophoblasts

How (5′S) and (5′R) 5′,8-Cyclo-2′-Deoxypurines Affect Base Excision Repair of Clustered DNA Damage in Nuclear Extracts of xrs5 Cells? A Biochemical Study

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