In a neutral pH range, pH 5 to 9, DNA molecules are quite stable. However, if the pH becomes too acidic or alkaline, DNA molecules are prone to destabilization.

At pH 5 or lower, DNA is liable to depurination (i.e. the loss of purine bases from DNA). The phosphodiester bonds of DNA break which causes the base pairs of DNA to break off.

At pH 9 or higher, DNA is susceptible to alkaline denaturation due to the abundance of hydroxide ions. These negatively-charged ions remove hydrogen ions from the base pairs of DNA, thereby breaking the hydrogen bonds between and causing the DNA strands to denature. While less damaging in comparison to acidic pH levels, high alkaline pH levels can still result in depurination.