Chemical reaction of DNA with cross-linking agents: Influences of base permutation on chemical reactivity

Abstract

Certain psoralens can photoreact with the pyrimidine bases of DNA and form interstrand cross-links. In this communication, theoretical mechanism of the photoreaction of DNA with psoralens in the presence of near-ultraviolet light (320–400 nm, u.v.-A) is diagrammatically and quantitatively presented. The number of the receptor binding sites, the theorized photoreaction sites, can be estimated from the base composition of DNA if the extent of the photoreactivity of cytosine and the possibly steric hindrance effects of DNA double helix in photoreactivity can be experimentally determined. The photoreactivity of DNA can be expressed by the number of psoralens photobound. It is predicted that the photoreactivity of DNA is less than, or at most equal to, the number of receptor binding sites depending on the number of cross-links formed during photoreaction. The number of cross-links formed is the consequence of the base permutation which determines the constitution of cross-linking sites, and of the manners of psoralens intercalated in the stacked DNA bases. In addition, the formation of the cross-linking sites is also influenced by the photoreactivity of cytosine which is presently not understood. It is likely that theoretical mechanism of the chemical reaction of DNA with other cross-linking agents can be similarly hypothesized.