Nature Reviews Molecular Cell Biology | Review Article
Cells are continuously faced with endogenous stress (for example, during replication) and exogenous stress (for example, during exposure to ultraviolet radiation) that can ultimately lead to DNA damage. To preserve genomic integrity, cells have an arsenal of repair proteins that detect different types of damage and initiate the appropriate repair pathway or, if irreparable, induce cell cycle arrest and/or apoptosis. These responses need to be tightly regulated to ensure that repair pathways are only activated by genuine DNA damage and not, for example, in response to telomeres. This control is achieved by multiple levels of regulation, including checkpoint signalling, non-coding RNAs and post-translational modifications such as ubiquitylation. This article series explores the pathways that detect and repair different types of DNA damage, highlighting new control mechanisms in the DNA damage response and the implications of disrupted repair pathways for disease.