A new perspective on ATR's role in translesion synthesis

During DNA replication, the physical and functional coupling of DNA unwinding by the CMG helicase with the DNA synthesis components of the replisome promotes highly efficient replication of the genome. What happens when the replication fork stalls at a DNA lesion? Do translesion synthesis (TLS) DNA polymerases operate in close coordination with the replisome or function independent of it; e.g., in daughter strand gaps? Using noncancer human cell lines, Yoon and colleagues (doi:10.1101/gad.353474.125) show that TLS operates in close coordination with the replisome and that ATR stabilizes the replisome at stalled replication forks; thus, TLS protects against chromosomal instability.