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Articles

RMI1 Promotes DNA Replication Fork Progression and Recovery from Replication Fork Stress

Jay Yang, Lara O'Donnell, Daniel Durocher, Grant W. Brown
Jay Yang
aDepartment of Biochemistry and Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario, Canada
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Lara O'Donnell
bSamuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada
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Daniel Durocher
bSamuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada
cDepartment of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada
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Grant W. Brown
aDepartment of Biochemistry and Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario, Canada
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DOI: 10.1128/MCB.00255-12
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ABSTRACT

RMI1 is a member of an evolutionarily conserved complex composed of BLM and topoisomerase IIIα (TopoIIIα). This complex exhibits strand passage activity in vitro, which is likely important for DNA repair and DNA replication in vivo. The inactivation of RMI1 causes genome instability, including elevated levels of sister chromatid exchange and accelerated tumorigenesis. Using molecular combing to analyze DNA replication at the single-molecule level, we show that RMI1 is required to promote normal replication fork progression. The fork progression defect in RMI1-depleted cells is alleviated in cells lacking BLM, indicating that RMI1 functions downstream of BLM in promoting replication elongation. RMI1 localizes to subnuclear foci with BLM and TopoIIIα in response to replication stress. The proper localization of the complex requires a BLM-TopoIIIα-RMI1 interaction and is essential for RMI1 to promote recovery from replication stress. These findings reveal direct roles of RMI1 in DNA replication and the replication stress response, which could explain the molecular basis for its involvement in suppressing sister chromatid exchange and tumorigenesis.

FOOTNOTES

    • Received 27 February 2012.
    • Returned for modification 18 March 2012.
    • Accepted 18 May 2012.
    • Accepted manuscript posted online 29 May 2012.
  • Supplemental material for this article may be found at http://dx.doi.org/10.1128/MCB.00255-12.

  • Copyright © 2012, American Society for Microbiology. All Rights Reserved.
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RMI1 Promotes DNA Replication Fork Progression and Recovery from Replication Fork Stress
Jay Yang, Lara O'Donnell, Daniel Durocher, Grant W. Brown
Molecular and Cellular Biology Jul 2012, 32 (15) 3054-3064; DOI: 10.1128/MCB.00255-12

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RMI1 Promotes DNA Replication Fork Progression and Recovery from Replication Fork Stress
Jay Yang, Lara O'Donnell, Daniel Durocher, Grant W. Brown
Molecular and Cellular Biology Jul 2012, 32 (15) 3054-3064; DOI: 10.1128/MCB.00255-12
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