Direct Reversal of DNA Alkylation Damage

ChemInform ◽  
2006 ◽  
Vol 37 (20) ◽  
Author(s):  
Yukiko Mishina ◽  
Erica M. Duguid ◽  
Chuan He
Keyword(s):  
Dna Alkylation ◽  
Alkylation Damage

scholarly journals Evolutionary analysis indicates that DNA alkylation damage is a byproduct of cytosine DNA methyltransferase activity

2018 ◽  
Vol 50 (3) ◽  
pp. 452-459 ◽  
Author(s):  
Silvana Rošić ◽  
Rachel Amouroux ◽  
Cristina E. Requena ◽  
Ana Gomes ◽  
Max Emperle ◽  
...  
Keyword(s):  
Dna Methyltransferase ◽  
Dna Alkylation ◽  
Evolutionary Analysis ◽  
Methyltransferase Activity ◽  
Alkylation Damage

scholarly journals Real-time dynamics of mutagenesis reveal the chronology of DNA repair and damage tolerance responses in single cells

2018 ◽  
Vol 115 (28) ◽  
pp. E6516-E6525 ◽  
Author(s):  
Stephan Uphoff
Keyword(s):  
Dna Repair ◽  
Real Time ◽  
Molecular Mechanisms ◽  
Damage Tolerance ◽  
Single Cells ◽  
Dna Alkylation ◽  
Alkylation Damage ◽  
Time Dynamics ◽  
Dna Mismatches ◽  
The Creation

Evolutionary processes are driven by diverse molecular mechanisms that act in the creation and prevention of mutations. It remains unclear how these mechanisms are regulated because limitations of existing mutation assays have precluded measuring how mutation rates vary over time in single cells. Toward this goal, I detected nascent DNA mismatches as a proxy for mutagenesis and simultaneously followed gene expression dynamics in single Escherichia coli cells using microfluidics. This general microscopy-based approach revealed the real-time dynamics of mutagenesis in response to DNA alkylation damage and antibiotic treatments. It also enabled relating the creation of DNA mismatches to the chronology of the underlying molecular processes. By avoiding population averaging, I discovered cell-to-cell variation in mutagenesis that correlated with heterogeneity in the expression of alternative responses to DNA damage. Pulses of mutagenesis are shown to arise from transient DNA repair deficiency. Constitutive expression of DNA repair pathways and induction of damage tolerance by the SOS response compensate for delays in the activation of inducible DNA repair mechanisms, together providing robustness against the toxic and mutagenic effects of DNA alkylation damage.

scholarly journals Regulation of DNA Alkylation Damage Repair: Lessons and Therapeutic Opportunities

2017 ◽  
Vol 42 (3) ◽  
pp. 206-218 ◽  
Author(s):  
Jennifer M. Soll ◽  
Robert W. Sobol ◽  
Nima Mosammaparast
Keyword(s):  
Dna Alkylation ◽  
Alkylation Damage ◽  
Damage Repair

scholarly journals Repair of DNA Alkylation Damage by theEscherichia coliAdaptive Response Protein AlkB as Studied by ESI-TOF Mass Spectrometry

2010 ◽  
Vol 2010 ◽  
pp. 1-9 ◽  
Author(s):  
Deyu Li ◽  
James C. Delaney ◽  
Charlotte M. Page ◽  
Alvin S. Chen ◽  
Cintyu Wong ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Chemical Oxidation ◽  
Dna Alkylation ◽  
Reaction Products ◽  
Ionization Time ◽  
Alkylation Damage ◽  
Living Organisms ◽  
First Time ◽  
Dependent Mechanism

DNA alkylation can cause mutations, epigenetic changes, and even cell death. All living organisms have evolved enzymatic and non-enzymatic strategies for repairing such alkylation damage. AlkB, one of theEscherichia coliadaptive response proteins, uses an α-ketoglutarate/Fe(II)-dependent mechanism that, by chemical oxidation, removes a variety of alkyl lesions from DNA, thus affording protection of the genome against alkylation. In an effort to understand the range of acceptable substrates for AlkB, the enzyme was incubated with chemically synthesized oligonucleotides containing alkyl lesions, and the reaction products were analyzed by electrospray ionization time-of-flight (ESI-TOF) mass spectrometry. Consistent with the literature, but studied comparatively here for the first time, it was found that 1-methyladenine, 1,N6-ethenoadenine, 3-methylcytosine, and 3-ethylcytosine were completely transformed by AlkB, while 1-methylguanine and 3-methylthymine were partially repaired. The repair intermediates (epoxide and possibly glycol) of 3,N4-ethenocytosine are reported for the first time. It is also demonstrated thatO6-methylguanine and 5-methylcytosine are refractory to AlkB, lending support to the hypothesis that AlkB repairs only alkyl lesions attached to the nitrogen atoms of the nucleobase. ESI-TOF mass spectrometry is shown to be a sensitive and efficient tool for probing the comparative substrate specificities of DNA repair proteinsin vitro.

scholarly journals Structure-function relationships governing activity and stability of a DNA alkylation damage repair thermostable protein

2015 ◽  
Vol 43 (18) ◽  
pp. 8801-8816 ◽  
Author(s):  
Giuseppe Perugino ◽  
Riccardo Miggiano ◽  
Mario Serpe ◽  
Antonella Vettone ◽  
Anna Valenti ◽  
...  
Keyword(s):  
Structure Function ◽  
Dna Alkylation ◽  
Alkylation Damage ◽  
Damage Repair ◽  
Thermostable Protein

scholarly journals Fluorescence Monitoring of the Oxidative Repair of DNA Alkylation Damage by ALKBH3, a Prostate Cancer Marker

2016 ◽  
Vol 138 (11) ◽  
pp. 3647-3650 ◽  
Author(s):  
Andrew A. Beharry ◽  
Sandrine Lacoste ◽  
Timothy R. O’Connor ◽  
Eric T. Kool
Keyword(s):  
Prostate Cancer ◽  
Dna Alkylation ◽  
Cancer Marker ◽  
Alkylation Damage

scholarly journals Glutamine deficiency induces DNA alkylation damage and sensitizes cancer cells to alkylating agents through inhibition of ALKBH enzymes

PLoS Biology ◽  
2017 ◽  
Vol 15 (11) ◽  
pp. e2002810 ◽  
Author(s):  
Thai Q. Tran ◽  
Mari B. Ishak Gabra ◽  
Xazmin H. Lowman ◽  
Ying Yang ◽  
Michael A. Reid ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Alkylating Agents ◽  
Dna Alkylation ◽  
Alkylation Damage

scholarly journals Activity and regulation of archaeal DNA alkyltransferase. CONSERVED PROTEIN INVOLVED IN REPAIR OF DNA ALKYLATION DAMAGE.

2015 ◽  
Vol 290 (2) ◽  
pp. 885-885
Author(s):  
Giuseppe Perugino ◽  
Antonella Vettone ◽  
Giuseppina Illiano ◽  
Anna Valenti ◽  
Maria C. Ferrara ◽  
...  
Keyword(s):  
Dna Alkylation ◽  
Alkylation Damage ◽  
Dna Alkyltransferase
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