Daughter-strand gaps in DNA replication - substrates of lesion processing and initiators of distress signalling

Dealing with DNA lesions during genome replication is particularly challenging because damaged replication templates interfere with the progression of the replicative DNA polymerases and thereby endanger the stability of the replisome. A variety of mechanisms for the recovery of replication forks exist, but both bacteria and eukaryotic cells also have the option of continuing replication downstream of the lesion, leaving behind a daughter-strand gap in the newly synthesized DNA. In this review, we address the significance of these singlestranded DNA structures as sites of DNA damage sensing and processing at a distance from ongoing genome replication. We describe the factors controlling the emergence of daughter-strand gaps from stalled replication intermediates, the benefits and risks of their expansion and repair via translesion synthesis or recombinationmediated template switching, and the mechanisms by which they activate local as well as global replication stress signals. Our growing understanding of daughter-strand gaps not only identifies them as targets of fundamental genome maintenance mechanisms, but also suggests that proper control over their activities has important practical implications for treatment strategies and resistance mechanisms in cancer therapy.

Automated summary

Dealing with DNA lesions during genome replication is challenging, but repairing daughter-strand gaps through translesion synthesis or recombination-mediated template switching is crucial for genome maintenance. Proper control over the activities of daughter-strand gaps has important implications for cancer therapy.