Replication stress links structural and numerical cancer chromosomal instability

Rebecca A. Burrell, Sarah E. McClelland, David Endesfelder, Petra Groth, Marie-Christine Weller, Nadeem Shaikh, Enric Domingo, Nnennaya Kanu, Sally M. Dewhurst, Eva Gronroos, Su Kit Chew, Andrew J. Rowan, Arne Schenk, Michal Sheffer, Michael Howell, Maik Kschischo, Axel Behrens, Thomas Helleday, Jiri Bartek, Ian P. Tomlinson and Charles Swanton ()
Additional contact information
Rebecca A. Burrell: Cancer Research UK London Research Institute, 44 Lincoln’s Inn Fields, London WC2A 3LY, UK
Sarah E. McClelland: Cancer Research UK London Research Institute, 44 Lincoln’s Inn Fields, London WC2A 3LY, UK
David Endesfelder: Cancer Research UK London Research Institute, 44 Lincoln’s Inn Fields, London WC2A 3LY, UK
Petra Groth: Science for Life Laboratory, Karolinska Institutet, Box 1031, Stockholm S-171 21, Sweden
Marie-Christine Weller: Science for Life Laboratory, Karolinska Institutet, Box 1031, Stockholm S-171 21, Sweden
Nadeem Shaikh: Cancer Research UK London Research Institute, 44 Lincoln’s Inn Fields, London WC2A 3LY, UK
Enric Domingo: Molecular and Population Genetics and NIHR Biomedical Research Centre, The Wellcome Trust Centre for Human Genetics, Oxford OX3 7BN, UK
Nnennaya Kanu: Cancer Research UK London Research Institute, 44 Lincoln’s Inn Fields, London WC2A 3LY, UK
Sally M. Dewhurst: Cancer Research UK London Research Institute, 44 Lincoln’s Inn Fields, London WC2A 3LY, UK
Eva Gronroos: Cancer Research UK London Research Institute, 44 Lincoln’s Inn Fields, London WC2A 3LY, UK
Su Kit Chew: Cancer Research UK London Research Institute, 44 Lincoln’s Inn Fields, London WC2A 3LY, UK
Andrew J. Rowan: Cancer Research UK London Research Institute, 44 Lincoln’s Inn Fields, London WC2A 3LY, UK
Arne Schenk: University of Applied Sciences Koblenz, RheinAhrCampus, Joseph-Rovan-Allee 2, 53424 Remagen, Germany
Michal Sheffer: Weizmann Institute of Science
Michael Howell: Cancer Research UK London Research Institute, 44 Lincoln’s Inn Fields, London WC2A 3LY, UK
Maik Kschischo: University of Applied Sciences Koblenz, RheinAhrCampus, Joseph-Rovan-Allee 2, 53424 Remagen, Germany
Axel Behrens: Cancer Research UK London Research Institute, 44 Lincoln’s Inn Fields, London WC2A 3LY, UK
Thomas Helleday: Science for Life Laboratory, Karolinska Institutet, Box 1031, Stockholm S-171 21, Sweden
Jiri Bartek: Danish Cancer Society Research Center, Strandboulevarden 49, DK-2100 Copenhagen, Denmark
Ian P. Tomlinson: Molecular and Population Genetics and NIHR Biomedical Research Centre, The Wellcome Trust Centre for Human Genetics, Oxford OX3 7BN, UK
Charles Swanton: Cancer Research UK London Research Institute, 44 Lincoln’s Inn Fields, London WC2A 3LY, UK

Nature, 2013, vol. 494, issue 7438, 492-496

Abstract: A mechanism to explain chromosomal instability (CIN) in colorectal cancer is demonstrated; three new CIN-suppressor genes (PIGN, MEX3C and ZNF516) encoded on chromosome 18q are identified, the loss of which leads to DNA replication stress, resulting in structural and numerical chromosome segregation errors, which are shown to be identical to phenotypes seen in CIN cells.

Date: 2013
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DOI: 10.1038/nature11935

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