The dynamic regulation of unperturbed DNA replication by ubiquitin. Proteolytic and nonproteolytic mechanisms are depicted with light orange and light blue background, respectively, and gray if a determination is incomplete. (A) Overview of the primary events occurring during DNA replication. Activation of the active CMG helicase (CDC45, MCM hexamer, GINS complex) induces the recruitment of the sliding clamp PCNA (depicted in red), which serves as an interaction platform to tether DNA polymerases to chromatin (Moldovan et al., 2007). (B) Polymerase switches occurring in lagging strand synthesis are mediated by ubiquitylation. (C and D) Concomitant with DNA replication, nucleosomes are disassembled and reassembled in a semiconservative manner, incorporating newly synthesized histones, which requires nondegradative ubiquitylation. (E) Termination of chromosomal replication in yeast and Xenopus requires Cdc48/p97 for CMG eviction from the chromatin. Red crosses depict targets of proteasomal degradation, and red circles depict ubiquitin. Ac, acetylation; Sc, Saccharomyces cerevisiae; Xl, Xenopus laevis.