Incision Coordination in Nucleotide Excision Repair

This thesis aims to contribute to the understanding of the molecular mechanism that underlies one of the main DNA repair pathways in mammals, nucleotide excision rcpair. In chapter 1 the relevance of DNA repair in general is outlined. An overview of mammalian strategies to counteract DNA damage is provided, to show that an intricate network of repair machineries permanently guards the integrity of the genome. In discussing each repair pathway, attention is focussed on how DNA damage is removed and what protein fhetors arc required to accomplish this. Chapter I serves as a framework for chapter 2, in which one repair pathway, mammalian nucleotide excision repair, is discussed more extensively. In this chapter, a comprehensive oven,jew of the characteristics of each protein factor involved in nucleotide excision repair is given. Our own observations will be included in this overview, which will serve as a fundament to build a model that addresses the molecular steps that lead to DNA incisions around the damage, a key event in nucleotide excision repair. Additionally, a model will be presented for transcriptioncoupled repair, a phenomenon that accounts for the fast removal of DNA damage from actively transcribed template strands. The contributions of this thesis to the repair field are summarized in chapters 3, 4, 5, and 6. For implications of these data, other than those discussed in chapters 1 and 2, the reader is reterred to the discussion sections that conclude each of the latter chapters.