scholarly journals Searching for DNA Lesions: Structural Evidence for Lower- and Higher-Affinity DNA Binding Conformations of Human Alkyladenine DNA Glycosylase

Biochemistry ◽  
2011 ◽  
Vol 51 (1) ◽  
pp. 382-390 ◽  
Author(s):  
Jeremy W. Setser ◽  
Gondichatnahalli M. Lingaraju ◽  
C. Ainsley Davis ◽  
Leona D. Samson ◽  
Catherine L. Drennan
Keyword(s):  
Dna Binding ◽  
Dna Lesions ◽  
Dna Glycosylase ◽  
Alkyladenine Dna Glycosylase

Base excision repair mediated cascading triple-signal amplification for the sensitive detection of human alkyladenine DNA glycosylase

The Analyst ◽  
2019 ◽  
Vol 144 (9) ◽  
pp. 3064-3071 ◽  
Author(s):  
Huige Zhang ◽  
Lili Wang ◽  
Yi Xie ◽  
Xianwei Zuo ◽  
Hongli Chen ◽  
...  
Keyword(s):  
Base Excision Repair ◽  
Significant Role ◽  
Signal Amplification ◽  
Excision Repair ◽  
Dna Lesions ◽  
Sensitive Detection ◽  
Dna Glycosylase ◽  
Alkyladenine Dna Glycosylase ◽  
Base Excision

DNA glycosylase (DG) plays a significant role in repairing DNA lesions, and the dysregulation of DG activity is associated with a variety of human pathologies.

scholarly journals Base Excision and DNA Binding Activities of Human Alkyladenine DNA Glycosylase Are Sensitive to the Base Paired with a Lesion

2001 ◽  
Vol 276 (16) ◽  
pp. 13379-13387 ◽  
Author(s):  
Clint W. Abner ◽  
Albert Y. Lau ◽  
Tom Ellenberger ◽  
Linda B. Bloom
Keyword(s):  
Dna Binding ◽  
Dna Glycosylase ◽  
Alkyladenine Dna Glycosylase ◽  
Base Excision

scholarly journals Validation of the in vitro comet assay for DNA cross-links and altered bases detection

2021 ◽  
Author(s):  
Damián Muruzabal ◽  
Julen Sanz-Serrano ◽  
Sylvie Sauvaigo ◽  
Bertrand Treillard ◽  
Ann-Karin Olsen ◽  
...  
Keyword(s):  
Comet Assay ◽  
Human Health Risk ◽  
High Sensitivity ◽  
Dna Lesions ◽  
Dna Glycosylase ◽  
Vitro Assay ◽  
Cytotoxic Compound ◽  
Endonuclease Iii ◽  
Cross Links

AbstractMechanistic toxicology is gaining weight for human health risk assessment. Different mechanistic assays are available, such as the comet assay, which detects DNA damage at the level of individual cells. However, the conventional alkaline version only detects strand breaks and alkali-labile sites. We have validated two modifications of the in vitro assay to generate mechanistic information: (1) use of DNA-repair enzymes (i.e., formamidopyrimidine DNA glycosylase, endonuclease III, human 8-oxoguanine DNA glycosylase I and human alkyladenine DNA glycosylase) for detection of oxidized and alkylated bases as well as (2) a modification for detecting cross-links. Seven genotoxicants with different mechanisms of action (potassium bromate, methyl methanesulfonate, ethyl methanesulfonate, hydrogen peroxide, cisplatin, mitomycin C, and benzo[a]pyrene diol epoxide), as well as a non-genotoxic compound (dimethyl sulfoxide) and a cytotoxic compound (Triton X-100) were tested on TK-6 cells. We were able to detect with high sensitivity and clearly differentiate oxidizing, alkylating and cross-linking agents. These modifications of the comet assay significantly increase its sensitivity and its specificity towards DNA lesions, providing mechanistic information regarding the type of damage.

scholarly journals Isolating Contributions from Intersegmental Transfer to DNA Searching by Alkyladenine DNA Glycosylase

2013 ◽  
Vol 288 (34) ◽  
pp. 24550-24559 ◽  
Author(s):  
Mark Hedglin ◽  
Yaru Zhang ◽  
Patrick J. O'Brien
Keyword(s):  
Dna Glycosylase ◽  
Alkyladenine Dna Glycosylase

scholarly journals SUMO-1 regulates the conformational dynamics of Thymine-DNA Glycosylase regulatory domain and competes with its DNA binding activity

2011 ◽  
Vol 12 (1) ◽  
pp. 4 ◽  
Author(s):  
Caroline Smet-Nocca ◽  
Jean-Michel Wieruszeski ◽  
Hélène Léger ◽  
Sebastian Eilebrecht ◽  
Arndt Benecke
Keyword(s):  
Dna Binding ◽  
Conformational Dynamics ◽  
Binding Activity ◽  
Dna Glycosylase ◽  
Regulatory Domain ◽  
Thymine Dna Glycosylase ◽  
Dna Binding Activity

Target-mediated hyperbranched amplification for sensitive detection of human alkyladenine DNA glycosylase from HeLa cells

Talanta ◽  
2019 ◽  
Vol 194 ◽  
pp. 846-851 ◽  
Author(s):  
Lili Wang ◽  
Huige Zhang ◽  
Yi Xie ◽  
Hongli Chen ◽  
Cuiling Ren ◽  
...  
Keyword(s):  
Hela Cells ◽  
Sensitive Detection ◽  
Dna Glycosylase ◽  
Alkyladenine Dna Glycosylase

scholarly journals Human Alkyladenine DNA Glycosylase Employs a Processive Search for DNA Damage†

Biochemistry ◽  
2008 ◽  
Vol 47 (44) ◽  
pp. 11434-11445 ◽  
Author(s):  
Mark Hedglin ◽  
Patrick J. O’Brien
Keyword(s):  
Dna Damage ◽  
Dna Glycosylase ◽  
Alkyladenine Dna Glycosylase

Roles of Active-Site Amino Acid Residues in Specific Recognition of DNA Lesions by Human 8-Oxoguanine-DNA Glycosylase (OGG1)

2019 ◽  
Vol 123 (23) ◽  
pp. 4878-4887 ◽  
Author(s):  
Timofey E. Tyugashev ◽  
Yury N. Vorobjev ◽  
Alexandra A. Kuznetsova ◽  
Maria V. Lukina ◽  
Nikita A. Kuznetsov ◽  
...  
Keyword(s):  
Amino Acid ◽  
Active Site ◽  
Dna Lesions ◽  
Dna Glycosylase ◽  
Amino Acid Residues ◽  
Specific Recognition

scholarly journals Alkyladenine DNA glycosylase associates with transcription elongation to coordinate DNA repair with gene expression

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Nicola P. Montaldo ◽  
Diana L. Bordin ◽  
Alessandro Brambilla ◽  
Marcel Rösinger ◽  
Sarah L. Fordyce Martin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Genome Stability ◽  
Genome Instability ◽  
Excision Repair ◽  
Regulation Of Gene Expression ◽  
Direct Interaction ◽  
Dna Glycosylase ◽  
Pol Ii ◽  
Naked Dna ◽  
Alkyladenine Dna Glycosylase

AbstractBase excision repair (BER) initiated by alkyladenine DNA glycosylase (AAG) is essential for removal of aberrantly methylated DNA bases. Genome instability and accumulation of aberrant bases accompany multiple diseases, including cancer and neurological disorders. While BER is well studied on naked DNA, it remains unclear how BER efficiently operates on chromatin. Here, we show that AAG binds to chromatin and forms complex with RNA polymerase (pol) II. This occurs through direct interaction with Elongator and results in transcriptional co-regulation. Importantly, at co-regulated genes, aberrantly methylated bases accumulate towards the 3′end in regions enriched for BER enzymes AAG and APE1, Elongator and active RNA pol II. Active transcription and functional Elongator are further crucial to ensure efficient BER, by promoting AAG and APE1 chromatin recruitment. Our findings provide insights into genome stability maintenance in actively transcribing chromatin and reveal roles of aberrantly methylated bases in regulation of gene expression.

The Thymine−DNA Glycosylase Regulatory Domain: Residual Structure and DNA Binding†

Biochemistry ◽  
2008 ◽  
Vol 47 (25) ◽  
pp. 6519-6530 ◽  
Author(s):  
Caroline Smet-Nocca ◽  
Jean-Michel Wieruszeski ◽  
Vicky Chaar ◽  
Arnaud Leroy ◽  
Arndt Benecke
Keyword(s):  
Dna Binding ◽  
Dna Glycosylase ◽  
Regulatory Domain ◽  
Thymine Dna Glycosylase ◽  
Residual Structure
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