Yasemin Baris

INTRODUCTION In the paradigmatic case, transcriptional activation of protein-encoding genes by RNA Polymerase II (Pol II) entails several steps1–4. In an initial stage, enhancer-bound activators recruit a series of chromatin remodeling and modifying cofactors that together covalently modify histones for recognition by other factors and evict nucleosomes to expose DNA regulatory elements1–4.

Ratnayeke et al. reveal how cells duplicate DNA precisely once during a period in early S phase when CDT1 overlaps with fired replication origins. They find that, after licensing origins in G1, CDT1 suppresses DNA synthesis at fired origins until CDT1 is fully degraded to deter re-replication during the overlap.

Abstract Chromosome replication is performed by a complex and intricate ensemble of proteins termed the replisome, where the DNA polymerases Polδ and Polε, DNA polymerase α-primase (Polα) and accessory proteins including AND-1, CLASPIN and TIMELESS–TIPIN (respectively known as Ctf4, Mrc1 and Tof1–Csm3 in Saccharomyces cerevisiae) are organized around the CDC45–MCM–GINS (CMG) replicative helicase1,2,3,4,5,6,7.