Schematic of the effect of UBP7 deletion. During DNA replication in a wild-type cell, a small amount of single-stranded DNA is exposed by the replicative helicase, and this single-stranded DNA is coated rapidly by RPA. The histone chaperone Asf1 deposits nucleosomes onto the newly synthesized DNA, and Rad6-Bre1 is responsible for H2B monoubiquitination at Lys-123. In a ubp7Δ cell, the replication fork is not stabilized properly, and this leads to HU and cisplatin sensitivity and elevated H2B ubiquitination. If an ubp7Δ strain is treated with HU, then there is an increase in single-stranded DNA coated by RPA and a requirement for SGS1, MRC1, and MUS81 for viability.