Chromatin Dynamics and DNA Repair

DNA damage from endogenous and exogenous sources threatens the genome and the epigenome, requiring chromatin-based DNA damage response pathways (DDR) to operate within structurally and functionally diverse chromatin environments. DDR pathways are essential for sensing, processing and repairing DNA damage. We describe how chromatin dynamics, including those regulated by histone modifications, histone variants and chromatin-associated proteins, promote DNA repair within chromatin. We will also discuss how DNA damage regulates transcription, alters the chromatin environment and affects the mobility of chromosomes to promote the DDR, and how genome organization impacts DNA repair and chromosome translocations. Finally, we explore the use of site-specific DNA damage systems and methodologies to measure histone dynamics to study the DDR and chromatin. This chapter provides an overview of how the DDR operates within the chromatin landscape to maintain genome and epigenome integrity, functions critical for cellular homeostasis and averting diseases including cancer.