Control of cell cycle transcription during G1 and S phases

Key Points The G1–S transcriptional programme is robustly activated by positive feedback mechanisms, creating an 'all-or-none' switch that leads to cell cycle commitment. Inactivation of G1–S transcription in both yeast and humans involves negative feedback loops. The wave of G1–S transcripts consists of subgroups based on their function, timing and mechanism of regulation. G1–S transcription is mechanistically linked to the DNA replication checkpoint by shared transcription factors in both yeast and humans in order to promote genomic stability during replication stress. Systems level properties associated with G1 control, such as the commitment point to cell division, the temporal pattern of G1–S transcription and its response to genotoxic stress, are likely to be conserved across eukaryotes despite frequent lack of protein sequence homology within the regulatory network. Recent work revealed new insights into the temporal regulation of G1–S cell cycle transcription, during proliferation and in response to activation of the DNA replication checkpoint. This has established the importance of G1–S transcription for both cell cycle progression and the maintenance of genome stability. The accurate transition from G1 phase of the cell cycle to S phase is crucial for the control of eukaryotic cell proliferation, and its misregulation promotes oncogenesis. During G1 phase, growth-dependent cyclin-dependent kinase (CDK) activity promotes DNA replication and initiates G1-to-S phase transition. CDK activation initiates a positive feedback loop that further increases CDK activity, and this commits the cell to division by inducing genome-wide transcriptional changes. G1–S transcripts encode proteins that regulate downstream cell cycle events. Recent work is beginning to reveal the complex molecular mechanisms that control the temporal order of transcriptional activation and inactivation, determine distinct functional subgroups of genes and link cell cycle-dependent transcription to DNA replication stress in yeast and mammals.