Model for the protective role of ITPA against HAP-induced genotoxicity and mutagenesis.

<p>In the presence of functional ITPA, the accumulation of non-canonical nucleotides like dHAPTP is abrogated by the ITPase, thereby preventing their incorporation into DNA. In the absence of functional ITPase, dHAPTP accumulates in the precursor pool and is incorporated into DNA by the replicative DNA polymerases. Grey circles represent HAP accumulation in DNA. Slow excision of base analogs by an unknown nuclease/glycosylase results in the accumulation of single-strand DNA breaks, which triggers apoptosis. Increased levels of apoptosis contribute to the onset of degenerative diseases. In the absence of repair, HAP persists in DNA causing incorrect pairing with T or C, thus leading to the accumulation of mutations, which predisposes individuals to the development of cancer.