E2F activity is crucial for the G1/S transition and DNA replication in mammalian cells. The retinoblastoma (pRB) family of proteins is the primary negative regulator of E2F. Recent findings have begun to clarify distinct roles for E2F family members during cell cycle progression and have considerably broadened our understanding of E2F transcriptional control beyond S phase. In this review, we examine the relative contribution of two distinct subclasses of E2F to repression and activation and how this division of labor could explain the role of E2F in DNA damage and repair checkpoints as well as tumorigenesis.
