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Unchecked nick ligation can promote localized genome re-replication
Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics. Chromosome Replication Laboratory, The Francis Crick Institute, London, UK.ORCID iD: 0000-0002-8526-6224
Chromosome Replication Laboratory, Francis Crick Institute, London, United Kingdom.
2021 (English)In: Current Biology, ISSN 0960-9822, E-ISSN 1879-0445, Vol. 31, no 11, p. R710-R711Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
Elsevier, 2021. Vol. 31, no 11, p. R710-R711
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
URN: urn:nbn:se:umu:diva-186360DOI: 10.1016/j.cub.2021.03.043ISI: 000658932200005PubMedID: 34102115Scopus ID: 2-s2.0-85107917996OAI: oai:DiVA.org:umu-186360DiVA, id: diva2:1581686
Available from: 2021-07-23 Created: 2021-07-23 Last updated: 2024-07-02Bibliographically approved

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Johansson, Erik

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