Abstract
Proper regulation of DNA replication ensures the faithful transmission of genetic material essential for optimal cellular and organismal physiology. Central to this regulation is the activity of a set of enzymes that induce or reverse posttranslational modifications of various proteins critical for the initiation, progression, and termination of DNA replication. This is particularly important when DNA replication proceeds in cancer cells with elevated rates of genomic instability and increased proliferative capacities. Here, we describe how DNA replication in mammalian cells is regulated via the activity of the ubiquitin-proteasome system as well as the consequence of derailed ubiquitylation signaling involved in this important cellular activity.