| dc.description.abstract | Cells are continuously exposed to endogenous and exogenous sources of damage causing DNA double-strand breaks (DSBs). Unrepaired DSBs represent to most dangerous form of DNA damage that can result in cell death, mutations, or genomic instability, one of the hallmarks of tumorigenesis. In reaction to DNA damage, the cell activates the DNA damage response which senses the DSB and recruits DSB repair factors. DSBs can be repaired through several repair pathways but the main pathways are homologous recombination (HR) and non-homologous end joining (NHEJ). The choice of DSB repair pathway depends on the cell cycle phase but also the location of the DSB. In eukaryotes, there are two main chromatin domains; Heterochromatin and euchromatin, each defined by specific histone modifications, histone variants, and chromatin binding proteins. These pre-existing chromatin factors, as well as damage-induced chromatin factors that surround a DSB, have been found to play an important role in the choice of DSB repair pathway. The surrounding factors can selectively interact with or recruit DSB repair factors of a certain pathway thereby promoting the usage of that specific pathway. It has therefore been suggested that these heterochromatin and euchromatin-specific factors, together with the cell cycle, help to promote the DSB repair pathway that suits that specific DSB the best. In this report, I discuss the influence of chromatin environment on DSB repair. More specifically I focus on the difference in DSB repair in constitutive heterochromatin between humans, Drosophila, and mouse cells, DSB repair in facultative heterochromatin, and DSB repair in centromeres and euchromatin | |
