Bringing It All Together: Coupling Excision Repair to the DNA Damage Checkpoint

Nucleotide excision repair and the ATR ‐mediated DNA damage checkpoint are two critical cellular responses to the genotoxic stress induced by ultraviolet ( UV ) light and are important for cancer prevention. In vivo genetic data indicate that these global responses are coupled. Aziz Sancar et al . developed an in vitro coupled repair‐checkpoint system to analyze the basic steps of these DNA damage stress responses in a biochemically defined system. The minimum set of factors essential for repair‐checkpoint coupling include damaged DNA , the excision repair factors ( XPA , XPC , XPF ‐ ERCC 1, XPG , TFIIH , RPA ), the 5′‐3′ exonuclease EXO 1, and the damage checkpoint proteins ATR ‐ ATRIP and Top BP 1. This coupled repair‐checkpoint system was used to demonstrate that the ~30 nucleotide single‐stranded DNA (ss DNA ) gap generated by nucleotide excision repair is enlarged by EXO 1 and bound by RPA to generate the signal that activates ATR .