title: Cyclin E2 induces genomic instability by mechanisms distinct from cyclin E1.
abstract: 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 proportion of abnormal mitoses, micronuclei and chromosomal aberrations. Cyclin E2 induction of genomic instability by a mechanism distinct from cyclin E1 indicates that these two proteins have unique functions in a cancer setting.
authors: The Kinghorn Cancer Centre and Cancer Research Program, Garvan Institute of Medical Research, Sydney, NSW, Australia.
authors: C Elizabeth
authors: CE
authors: Caldon
authors: C Marcelo
authors: CM
authors: Sergio
authors: Andrew
authors: A
authors: Burgess
authors: Andrew J
authors: AJ
authors: Deans
authors: Robert L
authors: RL
authors: Sutherland
authors: Elizabeth A
authors: EA
authors: Musgrove
mesh_terms: D045744:Cell Line, Tumor; D019927:Cyclin E / Q000235:genetics* / Q000378:metabolism; D051357:Cyclin-Dependent Kinase 2 / Q000235:genetics / Q000378:metabolism; D016213:Cyclins / Q000235:genetics* / Q000378:metabolism; D004261:DNA Replication; D015972:Gene Expression Regulation, Neoplastic; D015894:Genome, Human; D042822:Genomic Instability; D006801:Humans; D008677:Metaphase; D048629:Micronuclei, Chromosome-Defective; D008856:Microscopy, Fluorescence; D008938:Mitosis; D015513:Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D050720:Retinoblastoma-Like Protein p107 / Q000235:genetics / Q000378:metabolism
chemical_list: C475820:CCNE1 protein, human; C503688:CCNE2 protein, human; D019927:Cyclin E; D016213:Cyclins; D015513:Oncogene Proteins; C493844:RBL1 protein, human; D050720:Retinoblastoma-Like Protein p107; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2
keywords: cyclin E1; cyclin E2; genomic instability; mitosis; p107