Recombination-dependent replication: new perspectives from site-specific fork barriers

Abstract

Replication stress (RS) is intrinsic to normal cell growth, is enhanced by exogenous factors and elevated in many cancer cells due to oncogene expression. Most genetic changes are a result of RS and the mechanisms by which cells tolerate RS has received considerable attention because of the link to cancer evolution and opportunities for cancer cell-specific therapeutic intervention. Site-specific replication fork barriers have provided unique insights into how cells respond to RS and their recent use has allowed a deeper understanding of the mechanistic and spatial mechanism that restart arrested forks and how these correlate with RS-dependent mutagenesis. Here we review recent data from site-specific fork arrest systems used in yeast and highlight their strengths and limitations.