Abstract
It has been a long-standing question how DNA damage repair proceeds in a nuclear environment where DNA is packaged into chromatin. Several decades of analysis combining in vitro and in vivo studies in various model organisms ranging from yeast to human have markedly increased our understanding of the mechanisms underlying chromatin disorganization upon damage detection and re-assembly after repair. Here, we review the methods that have been developed over the years to delineate chromatin alterations in response to DNA damage by focusing on the well-characterized Nucleotide Excision Repair (NER) pathway. We also highlight how these methods have provided key mechanistic insight into histone dynamics coupled to repair in mammals, raising new issues about the maintenance of chromatin integrity. In particular, we discuss how NER factors and central players in chromatin dynamics such as histone modifiers, nucleosome remodeling factors, and histone chaperones function to mobilize histones during repair.
Highlights
In the cell nucleus, DNA is packaged into chromatin, a complex nucleoprotein structure whose basic unit is the nucleosome [1]
Chromatin assembly coupled to Nucleotide Excision Repair (NER) can be monitored in vitro by supercoiling assays using damaged plasmids mixed with extracts from human cells, xenopus eggs or drosophila embryos that are supplemented with a radioactive desoxyribonucleotide
Identifying the molecular players in these processes has been the focus of intense research, providing interesting mechanistic insights into histone dynamics coupled to NER, which we describe
Summary
DNA is packaged into chromatin, a complex nucleoprotein structure whose basic unit is the nucleosome [1]. The nucleosome core particle is composed of approximately 146 base pairs of DNA wrapped around an octamer of histone proteins comprising a (H3–H4) tetramer flanked by two H2A–H2B dimers [2] Linker histones such as H1 and non-histone proteins associate with the nucleosomal fiber, contributing to the formation of higher-order chromatin structures and nuclear domains [3,4]. Beyond this basic organization, the chromatin fiber shows variations in its compaction level and in its elementary components due to the existence of histone variants and post-translational modifications (reviewed in [5,6,7,8]). We present our current knowledge of the mechanisms underlying these dynamics, with an emphasis on the role of specific histone modifications, nucleosome remodelers, and histone chaperones
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