Dealing with DNA damage: relationships between checkpoint and repair pathways.

Cell cycle checkpoint activation and DNA repair pathways govern genomic stability after genotoxic stress. Genotoxic insult results in activation of an interwoven network of DNA damage checkpoints and DNA repair pathways. Post-translational modifications on a number of proteins involved in both checkpoint activation and DNA repair play an important role in this cellular response. Genotoxic stress can induce a wide variety of DNA lesions. Among these DNA alterations are double-stranded breaks and single-stranded DNA gaps. Repair of these DNA alterations requires damage recognition and resection. Here we discuss how DNA repair and DNA damage checkpoints cooperate and deal with DNA damage. Processing of DNA lesions by structure-specific nucleases results in DNA-protein intermediates, which form the basis for checkpoint activation and DNA repair. Post-translational modifications like phosphorylation and ubiquitination modulate the DNA damage response in a spatial and temporal manner. Cell cycle-dependent regulation additionally plays a key role in the regulation of both DNA repair and checkpoint activation. We highlight recent advances in in vivo imaging that greatly expand our knowledge on the relationships between DNA damage checkpoints and DNA repair.