Role of the retinoblastoma tumor suppressor in the maintenance of genome integrity

The retinoblastoma tumor suppressor (RB) is functionally inactivated at high frequency in human cancers. Based on the role of RB as a negative regulator of cell cycle this event would be expected to contribute to deregulated proliferation. However, evidence suggests that loss of RB not only mediates aberrant proliferation, but compromises the fidelity of cell cycle transitions leading to a breakdown in genome integrity. This review is focused on the mechanisms underlying this facet of RB function and the contibution of this process to tumorigenesis.