G1 phase: components, conundrums, context.

Abstract

A eukaryotic cell must coordinate DNA synthesis and chromosomal segregation to generate a faithful replica of itself. These events are confined to discrete periods designated synthesis (S) and mitosis (M), and are separated by two gap periods (Gl and G2). A complete proliferative cycle entails sequential and regulated progression through G1, S, G2, and M phases. During G1, cells receive information from the extracellular environment and determine whether to proliferate or to adopt an alternate fate. Work in yeast and cultured mammalian cells has implicated cyclin dependent kinases (Cdks) and their cyclin regulatory partners as key components controlling G1. Unique cyclin/Cdk complexes are temporally expressed in response to extracellular signaling, whereupon they phosphorylate specific targets to promote ordered G1 progression and S phase entry. Cyclins and Cdks are thought to be required and rate-limiting for cell proliferation because manipulating their activity in yeast and cultured mammalian cells alters G1 progression. However, recent evidence suggests that these same components are not necessarily required in developing mouse embryos or cells derived from them. The implications of these intriguing observations for understanding G1 progression and its regulation are discussed.