Synthesis of DNA lesions and DNA-lesion-containing oligonucleotides for DNA-repair studies

DNA and RNA are the molecules which store the genetic information in every organism. Both macromolecules are severely damaged by a variety of exogenou s and endogenous events. This leads to a loss of genetic information. Main lesions are strand breaks, apurinic and apyrimidinic sites and a variety of DNA bases with an altered structure. The result of these DNA modifications are cell death, mutations and in the worst scenario carcinogenous growth. In order to study the effect of DNA lesions on the structure of the DNA dou ble helix, a variety of lesion building blocks were recently synthesized an d incorporated into oligonucleotides. In addition, oligonucleotides which c ontain DNA lesions at specific sites are the basis for a detailed investiga tion of repair mechanisms that were developed by organisms in order to coun teract the lethal effect of DNA damage. This review article describes the r ecent synthetic progress that has enabled the preparation of DNA lesion pho sphoramidite building blocks. The synthetic procedures employed for their p reparation and the methods used to incorporate these building blocks into o ligonucleotides are described. The biological effect of each particular les ion is briefly recapitulated.