A Microscopic Study of the DNA Damage Response

The integrity of the genome is continuously challenged by both endogenous and exogenous DNA damaging agents. These damaging agents can induce a wide variety of lesions in the DNA, such as double strand breaks (DSB), single strand breaks (SSB), oxidative lesions and pyrimidine dimers. The cell has evolved intricate DNA damage response (DDR) mechanisms to counteract the genotoxic effects of these lesions. The two main features of the DDR are cell-cycle checkpoint activation and, at the heart of the response, DNA repair. For both damage signalling and repair, chromatin remodelling is most likely a prerequisite. Here, we discuss current knowledge on chromatin remodelling with respect to the cellular response to DNA damage, with emphasis on the response to single strand damage resolved by nucleotide excision repair (NER). We will discuss the role of histone modifications as well as their displacement or exchange in NER and make a comparison with their requirement in transcription and DSB repair. INTRODUCTION Proper functioning of all living organisms depends on faithful maintenance of