ABSTRACT
It was initially assumed that our genetic material, i.e., DNA, being the master blueprint of the cell, would retain a high degree of fidelity. However, it was soon recognized that DNA is in fact a dynamic molecule, subject to constant molecular change (1). For example, early studies found that DNA is prone to considerable base loss, where the extent of depurination varies inversely with pH and where elevated temperature promotes depurination through an acid-catalyzed hydrolytic reaction (2,3). Because heat had previously been shown to promote genetic mutations at physiological pH (4), the biological significance of base loss was postulated early on. In this chapter, we cover the mechanisms of AP site formation, the biological consequences of unrepaired AP lesions in DNA, the structural and dynamical consequences of AP sites when present in duplex DNA, and the mechanisms by which cells recognize and process abasic damage in an effort to avoid genome instability, cellular lethality, and ultimately human disease.
