Replication fork regression and its regulation

Abstract

One major challenge during genome duplication is the stalling of DNA replication forks by various forms of template blockages. As these barriers can lead to incomplete replication, multiple mechanisms have to act concertedly to correct and rescue stalled replication forks. Among these mechanisms, replication fork regression entails simultaneous annealing of nascent and template strands, which leads to regression of replication forks and formation of four-way DNA junctions. In principle, this process can lead to either positive outcomes, such as DNA repair and replication resumption, or less desirable outcomes, such as misalignment between nascent and template DNA and DNA cleavage. While our understanding of replication fork regression and its various possible outcomes is still at an early stage, recent studies using combinational approaches in multiple organisms have begun to identify the enzymes that catalyze this DNA transaction and how these enzymes are regulated, as well as the specific manners by which fork regression can influence replication. This review summarizes these recent progresses. In keeping with the theme of this series of reviews, we focus on studies in yeast and compare to findings in higher eukaryotes. It is anticipated that these findings will form the basis for future endeavors to further elucidate replication fork remodeling and its implications for genome maintenance.

Keywords: DNA motor proteins; Smc5/6; checkpoint kinases; replication fork regression.