Chromatin remodeling in the UV-induced DNA damage response

Abstract

DNA damage interferes with transcription and replication, causing cell death, chromosomal aberrations or mutations, eventually leading to aging and tumorigenesis (Hoeijmakers, 2009). The integrity of DNA is protected by a network of DNA repair and associated signalling pathways, collectively called the DNA damage response (DDR) (Jackson & Bartek, 2009). Chromatin poses a barrier for DNA repair and as such plays a critical role in controlling DDR efficiency. Chromatin is modified to regulate access of repair proteins to DNA and needs also to be restored to its original configuration afterwards. Chromatin also serves as an optimal regulation platform for DNA repair by mediating signalling events, providing docking sites for signaling proteins and controlling their activity. The work that we describe in this thesis is focused on the role of chromatin remodelling in DDR, specifically the Nucleotide Excision Repair (NER) pathway.