Instability and decay of the primary structure of DNA

@article{Lindahl1993InstabilityAD,
  title={Instability and decay of the primary structure of DNA},
  author={Tomas Lindahl},
  journal={Nature},
  year={1993},
  volume={362},
  pages={709-715}
}
Although DNA is the carrier of genetic information, it has limited chemical stability. Hydrolysis, oxidation and nonenzymatic methylation of DNA occur at significant ratesin vivo, and are counteracted by specific DNA repair processes. The spontaneous decay of DNA is likely to be a major factor in mutagenesis, carcinogenesis and ageing, and also sets limits for the recovery of DNA fragments from fossils. 

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References

SHOWING 1-10 OF 83 REFERENCES
New class of enzymes acting on damaged DNA
TLDR
Endonucleases that specifically attack DNA containing pyrimidine dinners2 or apurinic sites have been isolated from many types of cells, and enzymes of these two types have been shown to be active in DNA repair in Escherichia coli by the isolation of repair-deficient mutant strains with defective endo-nucleases. Expand
Damage to DNA Caused by Hydrolysis
The covalent structure of DNA is unstable in aqueous solution. It tends to hydrolyze to its monomeric components, and they themselves are subject to various hydrolytic reactions. These processes areExpand
MutT protein specifically hydrolyses a potent mutagenic substrate for DNA synthesis
TLDR
A novel mechanism which prevents replicational errors by degrading a potent mutagenic substrate for DNA synthesis is reported, which indicates that elimination from the nucleotide pool of the oxidized form of guanine nucleotide is important for the high fidelity of DNA synthesis. Expand
DNA glycosylases, endonucleases for apurinic/apyrimidinic sites, and base excision-repair.
  • T. Lindahl
  • Biology, Medicine
  • Progress in nucleic acid research and molecular biology
  • 1979
Publisher Summary This chapter discusses that since DNA is the carrier of genetic information and spontaneous mutations occur only at low frequency, cellular DNA has often been regarded as anExpand
Spontaneous deamination of cytosine and 5-methylcytosine residues in DNA and replacement of 5-methylcytosine residues with cytosine residues.
TLDR
5-Methylcy- tosine (mSC) constitutes - 0.7-3% of the bases of all studied normal vertebrate cells or tissues and is found mostly in CpG dinucleotide sequences. Expand
Nonenzymatic methylation of DNA by S-adenosylmethionine in vitro.
TLDR
S-Adenosylmethionine was found to methylate DNA non-enzymatically to produce the same putative promutagenic and procarcinogenic lesions formed by carcinogenic chemical methylating agents, and may indicate the mechanism whereby methylated guanine is formed in the liver DNA of rats with chemically induced liver damage. Expand
Mutagenic deamination of cytosine residues in DNA
TLDR
It is shown that in bacteria which lack uracil-DNA glycosylase (Ung−) and cannot excise urACil residues from DNA, the rate of spontaneous transition at cytosine residues is raised to the hotspot rate at 5-methylcytosine residue. Expand
High frequency mutagenesis by a DNA methyltransferase
TLDR
The data support current models for the formation of a covalent complex between the methyltransferase and cytosine and suggest that the occurrence of mutational hot spots at CpG sites may not always be due to spontaneous deamination of 5-methylcytosine, but might also be initiated by enzymaticDeamination of cytosines and proceed through a C-->U-->T pathway. Expand
A sensitive genetic assay for the detection of cytosine deamination: determination of rate constants and the activation energy.
TLDR
The data suggest that agents which perturb DNA structure or facilitate direct protonation of cytosine may induce deamination at biologically significant rates, and the assay provides a means to directly test the hypothesis. Expand
Chromosome Damage and Repair
TLDR
This work focuses on the use of DNA Tumor Viruses as Model Systems for Studying Damage and Repair of Eukaryotic Chromosomes, and the role of protein "X" Synthesis in Mammalian Cells. Expand
...
1
2
3
4
5
...