Perspectives on PARPs in S Phase.

Accurate copying of DNA during S phase is essential for genome stability and cell viability. During genome duplication, the progression of the DNA replication machinery is challenged by limitations in nucleotide supply and physical barriers in the DNA template that include naturally occurring DNA lesions and secondary structures that are difficult to replicate. To ensure correct and complete replication of the genome, cells have evolved several mechanisms that protect DNA replication forks and thus maintain genome integrity and stability during S phase. One class of enzymes that have recently emerged as important in this process, and therefore as promising targets in anticancer therapy, are the poly(ADP-ribose) polymerases (PARPs). We review here the roles of these enzymes during DNA replication as well as their impact on genome stability and cellular viability in normal and cancer cells.