Mitotic Chromosome Condensation Mediated by the Retinoblastoma Protein Is Tumor-suppressive

Authors

Courtney H. Coschi, The University of Western Ontario
Alison L. Martens, The University of Western Ontario
Kieran Ritchie, The University of Western Ontario
Sarah M. Francis, The University of Western Ontario
Subrata Chakrabarti, The University of Western Ontario
Nathalie G. Berube, The University of Western Ontario
Frederick A. Dick, The University of Western Ontario

Document Type

Article

Publication Date

7-1-2010

Journal

Genes & Development

Volume

24

Issue

13

First Page

1351

Last Page

1363

URL with Digital Object Identifier

http://dx.doi.org/10.1101/gad.1917610

Abstract

Condensation and segregation of mitotic chromosomes is a critical process for cellular propagation, and, in mammals, mitotic errors can contribute to the pathogenesis of cancer. In this report, we demonstrate that the retinoblastoma protein (pRB), a well-known regulator of progression through the G1 phase of the cell cycle, plays a critical role in mitotic chromosome condensation that is independent of G1-to-S-phase regulation. Using gene targeted mutant mice, we studied this aspect of pRB function in isolation, and demonstrate that it is an essential part of pRB-mediated tumor suppression. Cancer-prone Trp53(-/-) mice succumb to more aggressive forms of cancer when pRB's ability to condense chromosomes is compromised. Furthermore, we demonstrate that defective mitotic chromosome structure caused by mutant pRB accelerates loss of heterozygosity, leading to earlier tumor formation in Trp53(+/-) mice. These data reveal a new mechanism of tumor suppression, facilitated by pRB, in which genome stability is maintained by proper condensation of mitotic chromosomes.