scholarly journals Histone deacetylase SIRT1 modulates and deacetylates DNA base excision repair enzyme thymine DNA glycosylase

2013 ◽  
Vol 456 (1) ◽  
pp. 89-98 ◽  
Author(s):  
Amrita Madabushi ◽  
Bor-Jang Hwang ◽  
Jin Jin ◽  
A-Lien Lu
Keyword(s):  
Dna Repair ◽  
Histone Deacetylase ◽  
Excision Repair ◽  
Dna Glycosylase ◽  
Repair Enzyme ◽  
Repair Gene ◽  
Thymine Dna Glycosylase ◽  
Dna Base Excision Repair ◽  
Dna Repair Gene ◽  
Base Excision

SIRT1 histone deacetylase interacts with the DNA repair enzyme thymine DNA glycosylase (TDG). SIRT1 inhibits TDG expression and deacetylates TDG to modulate TDG activity and substrate specificity. These interactions may mediate DNA repair, gene expression and drug cytotoxicity.

scholarly journals The Effect of Allopregnanolone on Enzymatic Activity of the DNA Base Excision Repair Pathway in the Sheep Hippocampus and Amygdala under Natural and Stressful Conditions

2020 ◽  
Vol 21 (20) ◽  
pp. 7762
Author(s):  
Tomasz Misztal ◽  
Paweł Kowalczyk ◽  
Patrycja Młotkowska ◽  
Elżbieta Marciniak
Keyword(s):  
Dna Repair ◽  
Enzymatic Activity ◽  
Mrna Expression ◽  
Base Excision Repair ◽  
Excision Repair ◽  
Dna Glycosylase ◽  
Repair Capacity ◽  
Dna Base Excision Repair ◽  
Dna Base ◽  
Base Excision

The neurosteroid allopregnanolone (AL) has many beneficial functions in the brain. This study tested the hypothesis that AL administered for three days into the third brain ventricle would affect the enzymatic activity of the DNA base excision repair (BER) pathway in the hippocampal CA1 and CA3 fields and the central amygdala in luteal-phase sheep under both natural and stressful conditions. Acute stressful stimuli, including isolation and partial movement restriction, were used on the last day of infusion. The results showed that stressful stimuli increased N-methylpurine DNA glycosylase (MPG), thymine DNA glycosylase (TDG), 8-oxoguanine glycosylase (OGG1), and AP-endonuclease 1 (APE1) mRNA expression, as well as repair activities for 1,N6-ethenoadenine (εA), 3,N4-ethenocytosine (εC), and 8-oxoguanine (8-oxoG) compared to controls. The stimulated events were lower in stressed and AL-treated sheep compared to sheep that were only stressed (except MPG mRNA expression in the CA1 and amygdala, as well as TDG mRNA expression in the CA1). AL alone reduced mRNA expression of all DNA repair enzymes (except TDG in the amygdala) relative to controls and other groups. DNA repair activities varied depending on the tissue—AL alone stimulated the excision of εA in the amygdala, εC in the CA3 and amygdala, and 8-oxoG in all tissues studied compared to controls. However, the excision efficiency of lesioned bases in the AL group was lower than in the stressed and stressed and AL-treated groups, with the exception of εA in the amygdala. In conclusion, the presented modulating effect of AL on the synthesis of BER pathway enzymes and their repair capacity, both under natural and stressful conditions, indicates another functional role of this neurosteroid in brain structures.

scholarly journals Molecular cloning and chromosomal localization of DNA sequences associated with a human DNA repair gene.

1985 ◽  
Vol 5 (2) ◽  
pp. 398-405 ◽  
Author(s):  
J S Rubin ◽  
V R Prideaux ◽  
H F Willard ◽  
A M Dulhanty ◽  
G F Whitmore ◽  
...  
Keyword(s):  
Dna Repair ◽  
Dna Sequences ◽  
Chromosomal Localization ◽  
Excision Repair ◽  
Repair Process ◽  
Human Cells ◽  
Gene Products ◽  
Repair Gene ◽  
Human Dna ◽  
Dna Repair Gene

The genes and gene products involved in the mammalian DNA repair processes have yet to be identified. Toward this end we made use of a number of DNA repair-proficient transformants that were generated after transfection of DNA from repair-proficient human cells into a mutant hamster line that is defective in the initial incision step of the excision repair process. In this report, biochemical evidence is presented that demonstrates that these transformants are repair proficient. In addition, we describe the molecular identification and cloning of unique DNA sequences closely associated with the transfected human DNA repair gene and demonstrate the presence of homologous DNA sequences in human cells and in the repair-proficient DNA transformants. The chromosomal location of these sequences was determined by using a panel of rodent-human somatic cell hybrids. Both unique DNA sequences were found to be on human chromosome 19.

Association of genetic polymorphism of the DNA base excision repair gene (APE-1 Asp/148 Glu) and HPV type (16/18) with the risk of cervix cancer in north Indian population

2008 ◽  
Vol 4 (2) ◽  
pp. 63-71 ◽  
Author(s):  
Mohammad Shekari ◽  
Ranbir Chander Sobti ◽  
Dor Mohammad Kordi Tamandani ◽  
Keyanoosh Malekzadeh ◽  
Pushpinder Kaur ◽  
...  
Keyword(s):  
Genetic Polymorphism ◽  
Base Excision Repair ◽  
Indian Population ◽  
Excision Repair ◽  
Cervix Cancer ◽  
North Indian Population ◽  
Repair Gene ◽  
Dna Base Excision Repair ◽  
Dna Base ◽  
Base Excision

scholarly journals Thymine DNA Glycosylase Can Rapidly Excise 5-Formylcytosine and 5-Carboxylcytosine

2011 ◽  
Vol 286 (41) ◽  
pp. 35334-35338 ◽  
Author(s):  
Atanu Maiti ◽  
Alexander C. Drohat
Keyword(s):  
Embryonic Development ◽  
Catalytic Mechanism ◽  
Excision Repair ◽  
Dna Demethylation ◽  
Oxidation Products ◽  
Dna Glycosylase ◽  
Thymine Dna Glycosylase ◽  
Active Demethylation ◽  
Active Dna Demethylation ◽  
Base Excision

Thymine DNA glycosylase (TDG) excises T from G·T mispairs and is thought to initiate base excision repair (BER) of deaminated 5-methylcytosine (mC). Recent studies show that TDG, including its glycosylase activity, is essential for active DNA demethylation and embryonic development. These and other findings suggest that active demethylation could involve mC deamination by a deaminase, giving a G·T mispair followed by TDG-initiated BER. An alternative proposal is that demethylation could involve iterative oxidation of mC to 5-hydroxymethylcytosine (hmC) and then to 5-formylcytosine (fC) and 5-carboxylcytosine (caC), mediated by a Tet (ten eleven translocation) enzyme, with conversion of caC to C by a putative decarboxylase. Our previous studies suggest that TDG could excise fC and caC from DNA, which could provide another potential demethylation mechanism. We show here that TDG rapidly removes fC, with higher activity than for G·T mispairs, and has substantial caC excision activity, yet it cannot remove hmC. TDG excision of fC and caC, oxidation products of mC, is consistent with its strong specificity for excising bases from a CpG context. Our findings reveal a remarkable new aspect of specificity for TDG, inform its catalytic mechanism, and suggest that TDG could protect against fC-induced mutagenesis. The results also suggest a new potential mechanism for active DNA demethylation, involving TDG excision of Tet-produced fC (or caC) and subsequent BER. Such a mechanism obviates the need for a decarboxylase and is consistent with findings that TDG glycosylase activity is essential for active demethylation and embryonic development, as are mechanisms involving TDG excision of deaminated mC or hmC.

A mammalian cell line deficient in activity of the DNA repair enzyme 5-hydroxymethyluracil-DNA glycosylase is resistant to the toxic effects of the thymidine analog 5-hydroxymethyl-2'-deoxyuridine

1992 ◽  
Vol 12 (12) ◽  
pp. 5536-5540
Author(s):  
R J Boorstein ◽  
L N Chiu ◽  
G W Teebor
Keyword(s):  
Dna Repair ◽  
Cell Line ◽  
Mammalian Cell ◽  
Dna Glycosylase ◽  
Mammalian Cell Line ◽  
Repair Enzyme ◽  
Thymidine Analog ◽  
Large Numbers ◽  
Mechanism Of Toxicity ◽  
Base Excision

We isolated a mutant mammalian cell line lacking activity for the DNA repair enzyme 5-hydroxymethyluracil-DNA glycosylase (HmUra-DNA glycosylase). The mutant was isolated through its resistance to the thymidine analog 5-hydroxymethyl-2'-deoxyuridine (HmdUrd). The mutant incorporates HmdUrd into DNA to the same extent as the parent line but, lacking the repair enzyme, does not remove it. The phenotype of the mutant demonstrates that the toxicity of HmdUrd does not result from substitution of thymine in DNA by HmUra but rather from the removal via base excision of large numbers of HmUra residues in DNA. This finding elucidates a novel mechanism of toxicity for a xenobiotic nucleoside. Furthermore, the isolation of this line supports our hypothesis that the enzymatic repairability of HmUra derives not from its formation opposite adenine via the oxidation of thymine, but rather from its formation opposite guanine as a product of the oxidation and subsequent deamination of 5-methylcytosine.

scholarly journals A yeast DNA repair gene partially complements defective excision repair in mammalian cells.

1988 ◽  
Vol 7 (10) ◽  
pp. 3245-3253 ◽  
Author(s):  
C. Lambert ◽  
L. B. Couto ◽  
W. A. Weiss ◽  
R. A. Schultz ◽  
L. H. Thompson ◽  
...  
Keyword(s):  
Dna Repair ◽  
Mammalian Cells ◽  
Excision Repair ◽  
Repair Gene ◽  
Dna Repair Gene

Enzymes acting at strand interruptions in DNA

1995 ◽  
Vol 347 (1319) ◽  
pp. 57-62 ◽  
Keyword(s):  
Dna Repair ◽  
Excision Repair ◽  
Alternative Pathway ◽  
Environmental Dna ◽  
Repair Process ◽  
Dna Base Excision Repair ◽  
Acute Response ◽  
Soluble Cell ◽  
Essential Form ◽  
Base Excision

Endogenous and environmental DNA-damaging agents often generate single-strand interruptions in DNA. The lesions trigger a complex set of cellular reactions. In most eukaryotic cells, cellular poly(ADPribose) formation is the most acute response to such damage. Recently, such events have been amenable to study with soluble cell-free extracts of human cells. These investigations clarify the modulating role on DNA repair by poly (ADP-ribose), and suggest that the primary function of this unusual polymer is to act as an antirecombinant agent. Similar biochemical studies of subsequent repair events have revealed a branched pathway for the ubiquitous DNA base excision-repair process. The alternative pathway provides the cell with back-up functions for individual steps in this essential form of DNA repair.

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