Lux ex tenebris: nucleotide resolution DNA repair and nucleosome mapping

Abstract

In recent years a great deal of progress has been made in understanding how the various DNA repair mechanisms function when DNA is assembled into chromatin. In the case of nucleotide excision repair, a core group of DNA repair proteins is required in vitro to observe DNA repair activity in damaged DNA devoid of chromatin structure. This group of proteins is not sufficient to promote repair in the same DNA when assembled into nucleosomes; the first level of chromatin compaction. Clearly other factors are required for efficient DNA repair of chromatin. For some time chromatin has been considered a barrier to be overcome, and inhibitory to DNA metabolic processes including DNA repair. However, an emerging picture suggests a fascinating link at the interface of chromatin metabolism and DNA repair. In this view these two fundamental processes are mechanistically intertwined and function in concert to bring about regulated DNA repair throughout the genome. Light from the darkness has come as a result of many elegant studies performed by a number of research groups. Here we describe two techniques developed in our laboratories which we hope have contributed to our understanding in this arena.