Impairment of the TFIIH-associated CDK-activating kinase selectively affects cell cycle-regulated gene expression in fission yeast.

The fission yeast Mcs6-Mcs2-Pmh1 complex, homologous to metazoan Cdk7-cyclin H-Mat1, has dual functions in cell division and transcription: as a partially redundant cyclin-dependent kinase (CDK)-activating kinase (CAK) that phosphorylates the major cell cycle CDK, Cdc2, on Thr-167; and as the RNA polymerase (Pol) II carboxyl-terminal domain (CTD) kinase associated with transcription factor (TF) IIH. We analyzed conditional mutants of mcs6 and pmh1, which activate Cdc2 normally but cannot complete cell division at restrictive temperature and arrest with decreased CTD phosphorylation. Transcriptional profiling by microarray hybridization revealed only modest effects on global gene expression: a one-third reduction in a severe mcs6 mutant after prolonged incubation at 36 degrees C.

A CDK-activating kinase network is required in cell cycle control and transcription in fission yeast.

Cyclin-dependent kinases (CDKs) involved in cell cycle control require activation by phosphorylation, but CDK-activating kinase (CAK) has diverged between metazoans and budding yeast. Fission yeast has two CAKs: the essential Mcs6 complex, homologous to the metazoan CDK7 complex implicated in cell cycle control and transcription; and Csk1, a nonessential ortholog of budding yeast Cak1. Both can activate the major CDK, Cdc2, but Csk1 can also activate Mcs6, so it was unclear whether the pathway is a linear cascade or a network.