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Haploinsufficiency of an RB-E2F1-Condensin II Complex Leads to Aberrant Replication and Aneuploidy
Cancer Discovery
  • Courtney H. Coschi, Western University
  • Charles A. Ishak, Western University
  • David Gallo, University of Toronto Faculty of Medicine
  • Aren Marshall, Western University
  • Srikanth Talluri, Western University
  • Jianxin Wang, Ontario Institute for Cancer Research
  • Matthew J. Cecchini, Western University
  • Alison L. Martens, Western University
  • Vanessa Percy, Western University
  • Ian Welch, Western University
  • Paul C. Boutros, Ontario Institute for Cancer Research
  • Grant W. Brown, University of Toronto Faculty of Medicine
  • Frederick A. Dick, Western University
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Genome instability is a characteristic of malignant cells; however, evidence for its contribution to tumorigenesis has been enigmatic. In this study, we demonstrate that the retinoblastoma protein, E2F1, and Condensin II localize to discrete genomic locations including major satellite repeats at pericentromeres. In the absence of this complex, aberrant replication ensues followed by defective chromosome segregation in mitosis. Surprisingly, loss of even one copy of the retinoblastoma gene reduced recruitment of Condensin II to pericentromeres and caused this phenotype. Using cancer genome data and gene-targeted mice, we demonstrate that mutation of one copy of RB1 is associated with chromosome copy-number variation in cancer. Our study connects DNA replication and chromosome structure defects with aneuploidy through a dosage-sensitive complex at pericentromeric repeats. © 2014 American Association for Cancer Research.

Citation Information
Courtney H. Coschi, Charles A. Ishak, David Gallo, Aren Marshall, et al.. "Haploinsufficiency of an RB-E2F1-Condensin II Complex Leads to Aberrant Replication and Aneuploidy" Cancer Discovery Vol. 4 Iss. 7 (2014) p. 840 - 853
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