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Topoisomerase 1-Mediated Removal of Ribonucleotides from Nascent Leading-Strand DNA.
Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
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2013 (English)In: Molecular Cell, ISSN 1097-2765, E-ISSN 1097-4164, Vol. 49, no 5, 1010-1015 p.Article in journal (Refereed) Published
Abstract [en]

RNase H2-dependent ribonucleotide excision repair (RER) removes ribonucleotides incorporated during DNA replication. When RER is defective, ribonucleotides in the nascent leading strand of the yeast genome are associated with replication stress and genome instability. Here, we provide evidence that topoisomerase 1 (Top1) initiates an independent form of repair to remove ribonucleotides from genomic DNA. This Top1-dependent process activates the S phase checkpoint. Deleting TOP1 reverses this checkpoint activation and also relieves replication stress and genome instability in RER-defective cells. The results reveal an additional removal pathway for a very common lesion in DNA, and they imply that the "dirty" DNA ends created when Top1 incises ribonucleotides in DNA are responsible for the adverse consequences of ribonucleotides in RNase H2-defective cells.

Place, publisher, year, edition, pages
Cell Press , 2013. Vol. 49, no 5, 1010-1015 p.
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-66607DOI: 10.1016/j.molcel.2012.12.021PubMedID: 23375499OAI: oai:DiVA.org:umu-66607DiVA: diva2:608064
Available from: 2013-02-26 Created: 2013-02-26 Last updated: 2017-12-06Bibliographically approved

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Marjavaara, LisetteChabes, Andrei
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