5.2 The chemical stability of DNA
There are two main features of DNA that make it susceptible to damage. The first is the linkage between the deoxyribose Cl’ atom and the base (Figure 3b), a bond that is highly susceptible to hydrolysis. The other feature of DNA that contributes to its chemical instability is the presence of a large number of oxygen and nitrogen atoms in the bases. We have seen earlier how the polarisation of bonds within the bases contributes to the availability of hydrogen-bonding sites, but it also means that bases are prone to attack from other chemicals. It is not only in DNA that bases are susceptible, but also in the cellular pool of DNA precursor molecules, i.e. free deoxyribonucleotide triphosphates (dNTPs), that are utilised for DNA synthesis.
The frequent and relentless assault on the chemical integrity of DNA in the cellular environment would, at first sight, appear to compromise its central function as the vehicle of genetic information. It is for this reason that there exists a complex set of DNA repair enzymes, which very effectively, in most cases, reverses the chemical damage. Here we will provide an overview of the types of DNA damage that occur and how certain agents can have mutational effects. The chemical events involved are outlined in Table 3 and each is described in the following sections.
Table 3 Types of DNA damage and the chemical events involved.
* The thickness of the arrows corresponds to the relative sensitivity to alkylation.