Loss of Rb launches cell cycle

The elusive cell cycle– transcription link cientists have known for years that transcription is repressed as cells enter mitosis, yet the mechanistic bridge between the two processes has eluded detection. Now, Jian Chen, Beat Suter (McGill University, Montreal, Canada), and colleagues find that Xpd, a component of the general transcription factor complex, TFIIH, regulates another member of the complex, Cdk7, and thereby controls both transcriptional activity and entry into mitosis. “We weren’t specifically looking at Xpd,” says Suter. “We picked up the gene in a screen for mutants that suppressed a cell cycle defect in Cdk7” in Drosophila . The group found that decreased amounts of Xpd promote Cdk7 cell cycle activity. Conversely, overexpression of Xpd appears to pull Cdk7 into TFIIH, where it activates transcription but is unavailable to stimulate entry into mitosis. The cells thus become blocked at the G2/M transition. The researchers found that Xpd protein levels ebb and flow with the cell cycle, disappearing in prometaphase when Cdk7 needs to be free from TFIIH. It is not yet clear if Xpd’s role linking transcription and the cell cycle is conserved in mammals, but Suter says they will tackle that question next. Additionally, the team is working to find out what initiates the cascade leading to Xpd degradation.