Cyclin E2 induces genomic instability by mechanisms distinct from cyclin E1
C Elizabeth Caldon, C Marcelo Sergio, Andrew Burgess, Andrew J Deans, Robert L Sutherland, Elizabeth A Musgrove
CELL CYCLE | TAYLOR & FRANCIS INC | Published : 2013
Cyclins E1 drives the initiation of DNA replication, and deregulation of its periodic expression leads to mitotic delay associated with genomic instability. Since it is not known whether the closely related protein cyclin E2 shares these properties, we overexpressed cyclin E2 in breast cancer cells. This did not affect the duration of mitosis, nor did it cause an increase in p107 association with CDK2. In contrast, cyclin E1 overexpression led to inhibition of the APC complex, prolonged metaphase and increased p107 association with CDK2. Despite these different effects on the cell cycle, elevated levels of either cyclin E1 or E2 led to hallmarks of genomic instability, i.e., an increased pro..View full abstract
Awarded by National Health and Medical Research Council of Australia
Awarded by Cancer Institute NSW
The authors thank Dr Will Hughes for his assistance with live cell microscopy, the MLC Flow Cytometry Facility for assistance with cell sorting, and Ms Christine Lee for assistance with some experiments and figure preparation. This research was supported by the National Health and Medical Research Council of Australia (481307, 535903, 427601), the Cancer Institute NSW (07/CDF/1-28, 11/CDF/3-26, 09/RIG/1-18), the Young Garvan Foundation, the Australian Cancer Research Foundation (ACRF Unit for the Molecular Genetics of Cancer), the Petre Foundation, and the RT Hall Trust. C. E. C. is a National Breast Cancer Foundation (Australia) and Cure Cancer Australia Fellow. A. B. is a Cancer Institute NSW Future Research Leader. A.J.D. is a National Breast Cancer Foundation (Australia) fellow. R. L. S. was a NHMRC Senior Principal Research Fellow. E. A. M. is a Cancer Institute NSW Fellow.