Spatial positive feedback at the onset of mitosis

Abstract

For the cell-division cycle to progress, hundreds of genes and proteins must be coordinately regulated. Systems-level studies of this cycle show that positive-feedback loops help to keep events in sync.

The cell cycle is a complex but orderly sequence of events that culminates in the production of two cells from one. In eukaryotes, the cycle is divided into four phases: cell growth in G1 phase, DNA replication in S phase, more growth in G2 phase, and cell division in mitosis or M phase. The system of regulators that drives transitions between phases is centred on the cyclin-dependent kinases (CDKs), enzymes that are activated when regulatory proteins called cyclins bind to them. The CDK network directly or indirectly orchestrates coordinated regulation of proteins and genes involved in essentially every aspect of cell function. The complexity of these regulatory events raises the question of what systems-level strategies keep the process temporally coherent — how does the maestro of the cell cycle generate a definitive downbeat? Writing in this issue, Skotheim et al.¹ and Holt et al.² examine different phases of the cell cycle in the budding yeast Saccharomyces cerevisiae, and their findings converge on the same answer: positive feedback.