The Effects of Replication Stress on S Phase Histone Management and Epigenetic Memory

When a cell divides, it must not only accurately duplicate its genome but also recapitulate its programme of gene expression. A significant body of evidence suggests that an important fraction of the information specifying the transcriptional programme of vertebrate cells is carried epigenetically by post-translational modifications of histone proteins. For such a system to operate, propagation of key histone marks must be coupled to replication such that they remain correctly associated with the underlying DNA sequence, despite the huge disruption to chromatin structure generated by unwinding the parental DNA strands. Focusing on vertebrate cells but drawing on experimental evidence from a wide range of systems, we will examine the evidence that histone mark propagation through replication contributes to transcriptional stability. We then discuss the emerging molecular mechanisms that ensure that histone recycling is tightly coupled to DNA replication, focusing on how parental histone proteins are chaperoned around the replication fork, and the strategies that ensure that this process is not disrupted by impediments to replication.