Roadworks of DNA damage bypass during and after replication

Abstract

Duplication of the genome must be faithfully carried out in proliferating cells. DNA replication is the stage in which DNA damage becomes truly dangerous and potentially causes cell death or genomic instability. DNA damage bypass mechanisms have evolved as the 'last minute' processes to protect the quality of genome replication from these risks. Damage bypass provides a highly flexible mechanism to tolerate various types of DNA damage during replication. Recent studies have highlighted that bypass mechanisms can be uncoupled from global genome replication: i.e., the time of action of DNA damage bypass is not fixed at a particular point during genome replication. Although DNA damage bypass mechanisms are conserved throughout organisms, their regulation is different between prokaryotes and eukaryotes. On one hand, the bypass mechanisms of prokaryotes are mainly dependent on upregulation of transcripts under the SOS regulon. On the other hand, in eukaryotes, DNA damage bypass is activated by ubiquitylation of the replication sliding clamp, PCNA. This review starts with our understanding of the basis of lesion-bypassing mechanisms in the bacterial system, advances to recent views of the molecular mechanisms underlying eukaryotic DNA damage bypass and specifically focuses on how the bypassing mechanisms provide temporally and structurally flexible functions. © The Japanese Environmental Mutagen Society.