DNA pyrimidine bases at 5′-TpA sites

DNA pyrimidine bases at 5′-TpA sites are specific dinucleotide sequences within the DNA double helix that serve as the primary molecular target for furocoumarin drugs, such as psoralens (Cimino et al., 1985). These sites, consisting of a thymine residue followed by an adenine residue in the 5′ to 3′ direction, provide an optimal structural and electronic environment for the intercalation of these planar molecules (Hearst, 1989). Upon activation by ultraviolet A (UVA) light, the intercalated psoralen reacts covalently with the 5,6-double bond of adjacent pyrimidine bases, primarily thymine, to form monoadducts and interstrand crosslinks. These covalent modifications physically impede the progression of DNA and RNA polymerases, thereby inhibiting DNA synthesis and gene expression (Bethea et al., 1999). This mechanism is utilized clinically in photochemotherapy (PUVA) to treat hyperproliferative skin disorders like psoriasis and malignancies such as cutaneous T-cell lymphoma by inducing cell cycle arrest and apoptosis. However, the induction of these DNA lesions also carries a risk of mutagenicity, which can lead to secondary skin cancers over prolonged treatment periods.

Other names

5′-TpA dinucleotide sequenceThymine-Adenine DNA sitesPsoralen-DNA intercalation sites5′-TpA step

Drugs intercalate between base pairs at 5′-TpA sites and, upon activation by ultraviolet A (UVA) light, form covalent monoadducts or interstrand crosslinks with pyrimidine bases (primarily thymine), thereby inhibiting DNA synthesis and cell proliferation (Cimino et al., 1985; Hearst, 1989).