scholarly journals Two-tiered enforcement of high-fidelity DNA ligation

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Percy P. Tumbale ◽  
Thomas J. Jurkiw ◽  
Matthew J. Schellenberg ◽  
Amanda A. Riccio ◽  
Patrick J O’Brien ◽  
...  
Keyword(s):  
Dna Damage ◽  
Oxidative Dna Damage ◽  
High Fidelity ◽  
Dna Ligases ◽  
Dna Junctions ◽  
Dna Base ◽  
Dna Strands ◽  
Dna Mismatches ◽  
Second Tier ◽  
Dna Substrate

AbstractDNA ligases catalyze the joining of DNA strands to complete DNA replication, recombination and repair transactions. To protect the integrity of the genome, DNA ligase 1 (LIG1) discriminates against DNA junctions harboring mutagenic 3′-DNA mismatches or oxidative DNA damage, but how such high-fidelity ligation is enforced is unknown. Here, X-ray structures and kinetic analyses of LIG1 complexes with undamaged and oxidatively damaged DNA unveil that LIG1 employs Mg2+-reinforced DNA binding to validate DNA base pairing during the adenylyl transfer and nick-sealing ligation reaction steps. Our results support a model whereby LIG1 fidelity is governed by a high-fidelity (HiFi) interface between LIG1, Mg2+, and the DNA substrate that tunes the enzyme to release pro-mutagenic DNA nicks. In a second tier of protection, LIG1 activity is surveilled by Aprataxin (APTX), which suppresses mutagenic and abortive ligation at sites of oxidative DNA damage.

Mammalian DNA base excision repair proteins: their interactions and role in repair of oxidative DNA damage

Toxicology ◽  
2003 ◽  
Vol 193 (1-2) ◽  
pp. 43-65 ◽  
Author(s):  
Tadahide Izumi ◽  
Lee R. Wiederhold ◽  
Gargi Roy ◽  
Rabindra Roy ◽  
Arun Jaiswal ◽  
...  
Keyword(s):  
Dna Damage ◽  
Base Excision Repair ◽  
Oxidative Dna Damage ◽  
Excision Repair ◽  
Dna Base Excision Repair ◽  
Dna Base ◽  
Base Excision

scholarly journals Repair of Oxidative DNA Damage and Cancer: Recent Progress in DNA Base Excision Repair

2014 ◽  
Vol 20 (4) ◽  
pp. 708-726 ◽  
Author(s):  
Timothy L. Scott ◽  
Suganya Rangaswamy ◽  
Christina A. Wicker ◽  
Tadahide Izumi
Keyword(s):  
Dna Damage ◽  
Base Excision Repair ◽  
Recent Progress ◽  
Oxidative Dna Damage ◽  
Excision Repair ◽  
Dna Base Excision Repair ◽  
Dna Base ◽  
Base Excision

scholarly journals Inducible Repair of Oxidative DNA Lesions in the Rat Brain after Transient Focal Ischemia and Reperfusion

2003 ◽  
Vol 23 (11) ◽  
pp. 1324-1339 ◽  
Author(s):  
Jing Lan ◽  
Wenjin Li ◽  
Feng Zhang ◽  
Feng-Yan Sun ◽  
Tetsuya Nagayama ◽  
...  
Keyword(s):  
Dna Damage ◽  
Oxidative Dna Damage ◽  
Focal Ischemia ◽  
Artery Occlusion ◽  
Dna Lesions ◽  
Ischemia And Reperfusion ◽  
Dna Base ◽  
Ap Sites ◽  
Cerebral Artery Occlusion ◽  
Ap Site

To determine the role of oxidative DNA damage and repair in brain injury after focal ischemia and reperfusion, the authors investigated DNA base damage and DNA base excision repair (BER) capacity, the predominant repair mechanism for oxidative DNA lesions, in the rat model of temporary middle cerebral artery occlusion. Contents of 8-hydroxyl-2′-deoxyguanosine (8-oxodG) and apurinic/apyrimidinic abasic site (AP site), hallmarks of oxidative DNA damage, were quantitatively measured in nuclear DNA extracts from brains 0.25 to 72 hours after 1 hour of middle cerebral artery occlusion. In parallel to the detection of DNA lesions, the capacity for 8-oxodG- or AP site-dependent DNA repair synthesis was measured in nuclear protein extracts using specific in vitro DNA repair assays. After postischemic reperfusion, the levels of 8-oxodG and AP sites were markedly increased in ischemic tissues. In frontal/parietal cortex, regions that survived ischemia, 8-oxodG and AP sites were efficiently repaired during reperfusion. However, in the caudate, a region that was destined to infarct, the DNA lesions were poorly repaired. In consistent with the patterns of endogenous lesion repair, a markedly induced and long-lasting (at least 72 hours) BER activity was detected in the cortex but not in the caudate after ischemia. The induced BER activity in ischemic cortex was attributed to the upregulation of gene expression and activation of selective BER enzymes, particularly DNA polymerase-β and OGG1. These results strongly suggest that inducible DNA BER constitutes an important endogenous mechanism that protects brain against ischemia-induced oxidative neuronal injury.

Acrylamide Exposure and Oxidative DNA Damage, Lipid Peroxidation and Fasting Plasma Glucose Alteration: Association and Mediation Analyses in Chinese Urban Adults

2020 ◽  
Author(s):  
Bin Wang ◽  
Weihong Qiu ◽  
Shijie Yang ◽  
Limin Cao ◽  
Chunmei Zhu ◽  
...  
Keyword(s):  
Lipid Peroxidation ◽  
Dna Damage ◽  
Plasma Glucose ◽  
Fasting Plasma Glucose ◽  
Oxidative Dna Damage ◽  
Adult Population ◽  
Prostaglandin F2α ◽  
Mediation Analyses ◽  
Mediating Role ◽  
Fasting Plasma

<a><b>OBJECTIVE: </b></a>Acrylamide exposure from daily-consumed food has raised global concern.<b> </b>We aimed to assess the exposure-response relationships of internal acrylamide exposure with oxidative DNA damage, lipid peroxidation and fasting plasma glucose (FPG) alteration, and investigate the mediating role of oxidative DNA damage and lipid peroxidation in the association of internal acrylamide exposure with FPG. <p><b>RESEARCH DESIGN AND METHODS:</b> FPG and urinary biomarkers of oxidative DNA damage (8-hydroxy-deoxy-guanosine, 8-OHdG), lipid peroxidation (8-iso-prostaglandin-F2α, 8-iso-PGF2α) and acrylamide exposure (N-acetyl-S-(2-carbamoylethyl)-L-cysteine, AAMA; N-acetyl-S-(2-carbamoyl-2-hydroxyethyl)-L-cysteine, GAMA) were measured for 3,270 general adults from the Wuhan-Zhuhai cohort. The associations of urinary acrylamide metabolites with 8-OHdG, 8-iso-PGF2α and FPG were assessed by linear mixed models. The mediating roles of 8-OHdG and 8-iso-PGF2α were evaluated by mediation analysis.</p> <p><b>RESULTS:</b> We found significant linear positive dose-response relationships of urinary acrylamide metabolites with 8-OHdG, 8-iso-PGF2α and FPG (except GAMA with FPG), and 8-iso-PGF2α with FPG. Each 1-unit increase in log-transformed level of AAMA, ΣUAAM (AAMA+GAMA) or 8-iso-PGF2α was associated with a 0.17-, 0.15- or 0.23-mmol/L increase in FPG, respectively (<i>P </i>or/and<i> P trend</i><0.05). Each 1% increase in AAMA, GAMA or ΣUAAM was associated with a 0.19%, 0.27% or 0.22% increase in 8-OHdG, respectively, and a 0.40%, 0.48% or 0.44% increase in 8-iso-PGF2α, respectively (<i>P </i>and<i> P trend</i><0.05). Increased 8-iso-PGF2α rather than 8-OHdG significantly mediated 64.29% and 76.92% of the AAMA and ΣUAAM associated-FPG increases, respectively.</p> <p><b>CONCLUSIONS:</b> Exposure of general adult population to acrylamide was associated with FPG elevation, oxidative DNA damage and lipid peroxidation, which in turn partly mediated acrylamide-associated FPG elevation.<b></b></p>

Serum of 8-OHdG as a potential biomarker of oxidative DNA damage in workers exposed to harmful working environments

2020 ◽  
pp. 783-783
Author(s):  
I. A. Umnyagina ◽  
L. A. Strakhova ◽  
T. V. Blinova
Keyword(s):  
Oxidative Stress ◽  
Dna Damage ◽  
Blood Serum ◽  
Oxidative Dna Damage ◽  
Working Environment ◽  
Working Environments ◽  
Potential Biomarker ◽  
High Level ◽  
Damage Marker

In the blood serum of 70% individuals exposed to harmful factors of the working environment, a high level of oxidative stress and the DNA damage marker 8-Hydroxy-2’-Deoxyguanosine (8-OHdG) were detected.

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