Unchecked nick ligation can promote localized genome re-replication.

Current Biology : CB
Erik Johansson, J. F. X. Diffley

Abstract

Single-stranded DNA breaks, or nicks, are amongst the most common forms of DNA damage in cells. They can be repaired by ligation; however, if a nick occurs just ahead of an approaching replisome, the outcome is a collapsed replication fork comprising a single-ended double-strand break and a 'hybrid nick' with parental DNA on one side and nascent DNA on the other (Figure 1A). We realized that in eukaryotic cells, where replication initiates from multiple replication origins, a fork from an adjacent origin can promote localized re-replication if the hybrid nick is ligated. We have modelled this situation with purified proteins in vitro and have found that there is, indeed, an additional hazard that eukaryotic replisomes face. We discuss how this problem might be mitigated.

References

Apr 8, 2000·Trends in Biochemical Sciences·K J Marians
Oct 16, 2007·Nature Structural & Molecular Biology·Katsuhiro HanadaRoland Kanaar
Mar 6, 2015·Nature·Joseph T P YeelesJohn F X Diffley
Dec 3, 2015·Molecular Cell·Sebastian EustermannDavid Neuhaus
Dec 19, 2016·Molecular Cell·Joseph T P YeelesJohn F X Diffley
May 1, 2020·Frontiers in Microbiology·Aisha H SyedaChristian J Rudolph

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