Studies of the structure and stability of base pair mismatches, base pairs involving modified bases, and DNA-drug complexes

Abstract

Of the DNA bases, the hydrogen bonding characteristics of guanine (G) are complementary only to those of cytidine (C) and, similarly, the hydrogen bonding characteristics of adenine (A) are complementary only to those of thymine (T) (Fig. 1). This is the fundamental basis of Watson-Crick base pairing in DNA and ensures the extremely high fidelity of DNA replication which is essential in maintaining the integrity of living organisms. However, point mutations can, and do, occur and are the result of the formation of base pair mismatches between the native DNA bases during DNA synthesis or the misinsertion of a base by DNA polymerases caused by the presence of modified DNA bases in the template strand 9 There are two types of point mutation, known as transitions and transversions (Fig. 2). Transition mutations arise as a result of purine, pyrimidine mispairs and in this case one purine is replaced by the other purine or one pyrimidine by the other pyrimidine. In transversion mutations a purine is substituted by a pyrimidine and vice versa 9 This type of mutation is a consequence of purine.purine or pyrimindine.pyrimidine mismatches. In order for a base mispair to survive until the next round of DNA replication it must evade two checking procedures. The first occurs as each nucleoside triphosphate is incorporated into the newly synthesized DNA while the second, post-synthetic, step is a proofreading