Posttranslational protein modifiers of the ubiquitin family play a crucial role in many aspects of genome stability. In particular, tolerance to replication-blocking DNA lesions in eukaryotes is achieved by the ubiquitylation of the sliding clamp protein PCNA, an essential processivity factor for replicative DNA polymerases (1). While polyubiquitylation of PCNA facilitates an error-free damage avoidance mechanism that makes use of the genetic information encoded by the undamaged sister chromatid, we have shown that monoubiquitylation of the clamp activates specialised, damage-tolerant polymerases for mutagenic lesion bypass (2). Thus, differential modification of PCNA influences not only the efficiency, but also the accuracy of DNA replication in the presence of DNA-damaging agents. During S phase in the absence of exogenous DNA damage PCNA from budding yeast is modified by the ubiquitin-like protein SUMO, which in turn recruits a helicase, Srs2, to replication fork, thereby preventing unscheduled recombination events (3). I will describe the mechanisms by which the two modifiers cooperate in Saccharomyces cerevisiae and change the properties of the clamp, and I will discuss our observations that give insight into the cellular signals necessary for PCNA modifications.