Fig. 2

Resolution of replication stress. Impediments to replication fork progression lead to the generation of extended ssDNA tracts that initiate replication stress response. Recognition of ssDNA tracts by RPA serves as a signaling platform to trigger the ATR-CHK1 pathway (a). Once activated, this pathway triggers cell cycle arrest by inhibiting late origin firing. At the same time, activated CHK2 kinase acts through downstream effectors to promote processes crucial to restarting the stalled replication and preventing fork collapse, such as elevated dNTP production, DNA repair and nuclease activities. Lower illustrations show schematic representations of how replication stress may be resolved by indicated key factors; resolution of UV damage (b) and TRCs (c) are depicted