Lundin, C., North, M., Erixon, K. et al. (4 more authors) (2005) Methyl methanesulfonate (MMS) produces heat-labile DNA damage but no detectable in vivo DNA double-strand breaks. NUCLEIC ACIDS RESEARCH, 33 (12). pp. 3799-3811. ISSN 0305-1048
Abstract
Homologous recombination (HR) deficient cells are sensitive to methyl methanesulfonate (MMS). HR is usually involved in the repair of DNA double-strand breaks (DSBs) in Saccharomyces cerevisiae implying that MMS somehow induces DSBs in vivo. Indeed there is evidence, based on pulsed-field gel electrophoresis (PFGE), that MMS causes DNA fragmentation. However, the mechanism through which MMS induces DSBs has not been demonstrated. Here, we show that DNA fragmentation following MMS treatment, and detected by PFGE is not the consequence of production of cellular DSBs. Instead, DSBs seen following MMS treatment are produced during sample preparation where heat-labile methylated DNA is converted into DSBs. Furthermore, we show that the repair of MMS-induced heat-labile damage requires the base excision repair protein XRCC1, and is independent of HR in both S.cerevisiae and mammalian cells. We speculate that the reason for recombination-deficient cells being sensitive to MMS is due to the role of HR in repair of MMS-induced stalled replication forks, rather than for repair of cellular DSBs or heat-labile damage.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | Copyright © The Author 2005. Published by Oxford University Press. All rights reserved The online version of this article has been published under an open access model. Users are entitled to use, reproduce, disseminate, or display the open access version of this article for non-commercial purposes provided that: the original authorship is properly and fully attributed; the Journal and Oxford University Press are attributed as the original place of publication with the correct citation details given; if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative work this must be clearly indicated. For commercial re-use, please contact gro.slanruojpuo@snoissimrep.slanruoj |
Keywords: | SISTER-CHROMATID EXCHANGE; STALLED REPLICATION FORKS; CULTURED MAMMALIAN CELLS; BASE EXCISION-REPAIR; SACCHAROMYCES-CEREVISIAE; HOMOLOGOUS RECOMBINATION; CHROMOSOMAL INSTABILITY; DEOXYRIBONUCLEIC ACID; ALKYLATING-AGENTS; SENSITIVE MUTANTS |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Science (Sheffield) > School of Biosciences (Sheffield) > Department of Molecular Biology and Biotechnology (Sheffield) The University of Sheffield > Faculty of Science (Sheffield) > School of Mathematics and Statistics (Sheffield) |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 05 Aug 2016 10:41 |
Last Modified: | 05 Aug 2016 10:41 |
Published Version: | http://dx.doi.org/10.1093/nar/gki681 |
Status: | Published |
Publisher: | Oxford University Press |
Refereed: | Yes |
Identification Number: | 10.1093/nar/gki681 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:95015 |