The involvement of cyclin-dependent kinase 7 (CDK7) and 9 (CDK9) in coordinating transcription and cell cycle checkpoint regulation

Abstract

Cells regulate the expression of cell cycle-related genes, including cyclins essential for mitosis, through the transcriptional activity of the positive transcription elongation factor b (P-TEFb), a complex comprising CDK9, cyclin T, and transcription factors. P-TEFb cooperates with CDK7 to activate RNA polymerase. In response to DNA stress, the cell cycle shifts from mitosis to repair, triggering cell cycle arrest and the activation of DNA repair genes. This tight coordination between transcription, cell cycle progression, and DNA stress response is crucial for maintaining cellular integrity. Cyclin-dependent kinases CDK7 and CDK9 are central to both transcription and cell cycle regulation. CDK7 functions as the CDK-activating kinase (CAK), essential for activating other CDKs, while CDK9 acts as a critical integrator of signals from both the cell cycle and transcriptional machinery. This review elucidates the mechanisms by which CDK7 and CDK9 regulate the mitotic process and cell cycle checkpoints, emphasizing their roles in balancing cell growth, homeostasis, and DNA repair through transcriptional control.

Keywords: CDK7; CDK9; Cell cycle; transcription.

Figure 1.

CDKs and cyclins orchestrate the cell cycle, with CDK4/6 partnering with cyclin D during the G1 phase, and CDK2 with cyclin E and cyclin a at the G1/S checkpoint and S phase. CDK1 collaborating cyclin a and cyclin B in the G2 phase and checkpoint for M phase.

Figure 2.

Regulation of CDK9 transcription activity by CDK7.

Figure 3.

The involvement of the CDK9-55kDa isoform in DNA stress response.

Figure 4.

Proposed Model: a role for CDK9 in coordinating transcription and Cell Cycle Regulation. We hypothesize that CDK9 shifts between isoforms to manage transcription regulation and DNA stress response effectively.