DNA Excision Repair at the Nucleosome Level of Chromatin

Abstract

The complexity of enzymatic mechanisms that have evolved for the recognition and removal of DNA lesions in mammalian cells is undoubtedly coupled to the complexity of the very “substrate” itself (i.e., the highly condensed structure of DNA in chromatin). For this reason, over the past decade my laboratory has focused on the role of chromatin structure in the process of excision repair in eukaryotes. In the discussion that follows, I have reviewed our results concerning features of DNA damage formation and excision repair at the nucleosome level of chromatin. It is important to keep in mind that the features discussed are reflective primarily of “bulk” (i.e., transcriptionally inactive) chromatin in mammalian cells. The discussion starts with a brief review of nucleosome structure, and ends with a rather simple, generalized model for excision repair of DNA in bulk chromatin of mammalian cells. Throughout this chapter, I have cited recent reviews, rather than specific papers, pertaining to a given topic. Specific references can be found in these reviews.