MELTING OF CROSS-LINKED DNA .1. MODEL AND THEORETICAL METHODS

Covalent and strong coordination binding to DNA of a large number of a ntitumour drugs and other compounds leads to interstrand cross-link fo rmation. To investigate cross-link influence on double helix stability , two methods are developed for the calculation of melting curves. The first method is based on Poland's approach. It requires computer time proportional to u.N, where u is the average distance (in base pairs) between neighboring crosslinks, and N is the number of base pairs in t he DNA chain. The method is more suitable when u is not large, and sma ll loops formed by interstrand cross-links in melted regions strongly affect DNA melting. The computer time for the second method, based on the Fixman-Freire approach, does not depend on the number of cross-lin ks and is proportional to 1.N (1 is the number of exponential function s used for a decomposition of the loop entropy factor). It is more app ropriate when N and u are large, and therefore particular values of th e entropy factors of small loops do not influence DNA melting behavior .