The Cockayne syndrome B protein: involvement in transcription-coupled DNA repair

Each organism stores its genetic information in large DNA molecules, present in most cells. DNA is composed of four different nucleotides, abbreviated as G,A,T,and C, which make up the genetic code that is translated into proteins. An intermediate between DNA and protein is the RNA, that is generated by a process called transcription, during which one strand of the double DNA helix serves as a template and is read by a scanning RNA polymerase complex. As a result, a messenger RNA molecule is produced, that in turn forms a template for protein synthesis. It is of major importance that changes (mutations) in the genetic code of the DNA are limited to a minimum. Although mutations form the basis of biological diversity, they can also be the starting point of carcinogenesis in multicellular species. The genomic DNA is continuously challenged by a variety of damaging agents, interfering with cellular processes that involve DNA metabolism. Of many of those reagents, the nature of the resulting lesion has been established. Various chemical compounds, inducing bulky adducts, and also UV-irradiation cause distortions and bending of the DNA helix. Ionising irradiation and oxygen radicals afe known to generate single and double strand breaks in the DNA, while exposure to alkylating agents can lead to various types of modification of single nucleotides. Also, intracellular processes can enhance the intrinsic instability of some of the DNA bonds and can lead to alterations in the DNA, e.g. via hydrolysis and oxidation. Mutations are generated if these modified nucleotides mispair during DNA replication (prior to cell division). which can also happen spontaneously. This will in many cases lead to incorporation of a wrong nucleotide, thus generating a 'mismatch' which, when wrongly processed, can lead to a change of the genetic code. All organisms have developed an intricate network of DNA repair modes to remove the lesions before they can exert their deleterious effects.