Instability and decay of the primary structure of DNA

  title={Instability and decay of the primary structure of DNA},
  author={Tomas Lindahl},
  • T. Lindahl
  • Published 22 April 1993
  • Biology, Chemistry
  • Nature
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. 

DNA Chemical Instability

DNA is a relatively unstable molecule that undergoes hydrolytic, oxidative and nonenzymatic degradation. Its instability places limitations on its survival in the geosphere yet enables its rapid

The Croonian Lecture, 1996: endogenous damage to DNA.

  • T. Lindahl
  • Biology
    Philosophical transactions of the Royal Society of London. Series B, Biological sciences
  • 1996
Although DNA is the carrier of stable genetic information, this giant molecule exhibits slow turnover in cells as a consequence of endogenous damage, some forms of endogenous DNA damage still cause mutagenic alterations and may result in human disease.

Structural Phylogenetics of DNA Base Excision Repair

The repair of DNA damage is fundamental to living organisms and is implicated for reactive oxygen and pathogen defenses, for controlling degenerative diseases and aging, and for the development of sex and meiosis.

Topoisomerase-Induced DNA Damage

This brief chapter gives an overview of the broad range of lesions that lead to the accumulation of cleavage complexes produced by DNA topoisomerases I and II.

Quality control by DNA repair.

In some cases, DNA damage is not repaired but is instead bypassed by specialized DNA polymerases, and the integrity of the genetic information is compromised.

DNA Structure: Inherent Instability and Genotoxic Reactions

The principal goal of this chapter is to provide examples of biologically significant lesions in DNA that are (1) chemically and structurally well characterized and (2) serve as experimental models

Specialized DNA Polymerases, Cellular Survival, and the Genesis of Mutations

Cell death caused by arrested replication of damaged or structurally altered DNA can be avoided in prokaryotic and eukaryotic cells by multiple DNA polymerases that are specialized to bypass DNA

Structure of a trapped endonuclease III–DNA covalent intermediate

The crystal structure of a trapped intermediate that represents EndoIII frozen in the act of repairing DNA is determined and suggests a rationale for the frequent occurrence in certain human cancers of a specific mutation in the related DNA repair protein MYH.



New class of enzymes acting on damaged DNA

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.

Damage to DNA Caused by Hydrolysis

The covalent structure of DNA is unstable in aqueous solution, and it tends to hydrolyze to its monomeric components, and they themselves are subject to various hydrolytic reactions, which can cause mutation or inactivate the DNA.

MutT protein specifically hydrolyses a potent mutagenic substrate for DNA synthesis

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.

DNA glycosylases, endonucleases for apurinic/apyrimidinic sites, and base excision-repair.

  • T. Lindahl
  • Biology
    Progress in nucleic acid research and molecular biology
  • 1979

Nonenzymatic methylation of DNA by S-adenosylmethionine in vitro.

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.

Mutagenic deamination of cytosine residues in DNA

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.

A sensitive genetic assay for the detection of cytosine deamination: determination of rate constants and the activation energy.

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.

Chromosome Damage and Repair

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.