Model for replication-associated interstrand crosslink repair in yeast. (A) Replication is stalled by an ICL, Rad5 polyubiquitylates PCNA, and Mph1-mediated fork-reversal stabilizes the fork for repair (with Smc5/6 and Mhf1/2) and protects the repair intermediates from collapsing into double strand breaks (DSBs). Downstream events of repair are mediated by Slx4 and Exo1. HR and TLS are important for gap-filling steps. The figure key shows the putative human homologs in brackets. (B) The basic steps of ICL repair lead to various fragile intermediates (ssDNA, single strand DNA) that can collapse into DSBs. Cell death is triggered if the DSB cannot be repaired.