Figure 6.

HDR and mutagenic TLS function sequentially and are regulated in concert with checkpoint signaling to maximize the potential for error-free post-replication repair. The DNA damage checkpoint response to UV delays mitosis to allow HDR to complete error-free PRR using redundant information within the sister chromatids. Rad51 recombinase is required to prevent mutagenic TLS by Rev1 and Polζ during the checkpoint delay. A pathway mediated by Rhp18, Rad8, and Polη makes a more limited contribution to PRR at CPDs during the checkpoint delay and may continue to function after the G2/M checkpoint (not shown). After the G2/M checkpoint, cells lose the capacity to complete HDR and rely on Rev1 and Polζ to restore the continuity of the double helix. We suggest that the structures repaired by Rev1 and Polζ are formed most frequently in regions of the genome that remain unreplicated after the G2/M checkpoint. Gaps may form in such regions when replication forks encounter lesions (post-replicative daughter-strand gaps) or when an unreplicated region is unwound during mitosis (mitotic daughter-stand gaps). Rev1 and Polζ may begin to function immediately after cells pass the G2/M checkpoint or, more likely, gain access to DNA when HDR is inactivated at the metaphase-to-anaphase transition.