Question

How does the dissociable Srb10/11 (Cdk8/CyclinC) module of Mediator repress (or inhibit initiation) transcription?

- Cdk8 phosphorylates Cyclin H of TFIIH (in the CAK). This prevents Cdk7 from phosphorylating Ser5 of the CTD.
- Mediator binds pTEFb, blocking the phosphorylation of Ser2 of the CTD.
-The Srb10/11 module binds the CTD, blocking its phosphorylation by TFIIH (CAK).
-Cdk7 of the CAK (TFIIH) phosphorylates Cyclin C. This prevents Mediator from activating transcription.

Answer 1

The Srb10/11 module of Mediator can repress transcription initiation through phosphorylation of Cyclin H by Cdk8, which inhibits Cdk7's activity on the CTD, as well as potentially inhibiting transcription activation by interaction with pTEFb and direct binding to the CTD.

Step-by-step explanation:

The dissociable Srb10/11 (Cdk8/CyclinC) module of Mediator can repress transcription initiation through several mechanisms. One of the modes of repression involves Cdk8 phosphorylating Cyclin H of TFIIH within the CDK-activating kinase (CAK) complex. This phosphorylation prevents Cdk7 from phosphorylating Ser5 on the C-terminal domain (CTD) of RNA polymerase II, a modification that is required for the initiation of transcription. Moreover, the Mediator complex binding to pTEFb can block the phosphorylation of Ser2 on the CTD, which is necessary for the transition into productive elongation.

Additionally, Srb10/11 can bind directly to the CTD, blocking its phosphorylation by TFIIH (CAK). Lastly, phosphorylation of Cyclin C by Cdk7 is another possible inhibitory mechanism, as it could prevent Mediator from activating transcription. However, this specific mechanism is not strongly supported by current evidence.