5) Questions about the Mediator of Transcription a) What do we mean when we say

Question

5) Questions about the Mediator of Transcription a) What do we mean when we say that the Mediator of Transcription is "functionally analogous" to the -CTD of the bacterial core polymerase? b) The SRB genes, which encode several of the subunits of the Mediator, were isolated in a screen for mutations that suppress the cold-sensitive phenotype resulting from truncation of the Pol Il CTD. Suppressor mutations in the Cdk8 gene (which encodes a part of the Mediator's Cdk8 module) were found to be recessive. This means that in a diploid yeast cell, both copies of the gene must carry the mutation before suppression of the cold-sensitive phenotype is observed. This indicates that the suppressor mutations are probably loss-of-function mutations (that is, they inactivate the Cdk8 module). Explain why this suggests that the Cdk8 module is an inhibitory module (i.e., that it inhibits Mediator function)? Suppressor mutations in genes encoding head module subunits tend to be dominant mutations, meaning that a suppressor mutation in one copy of the gene encoding the head module subunit is enough to suppress the cold-sensitive phenotype resulting from truncation of the Pol Il CTD even in the presence of a wild-type copy of the gene. This suggests that these mutations are likely gain-of-function mutations. In other words, rather than inactivating the encoded protein, they somehow make the protein more active. Recent findings indicate that the head module likely makes extensive contact with the Pol Il CTD. Suggest a mechanism by which the dominant suppressor mutation:s in head module genes might suppress the cold sensitive phenotype resulting from truncation of the Pol II CTD. c)

Explanation / Answer

a. Mediator of transcription is analogous to alpha- CTD of the bacterial core polymerase because these proteins have common sequence and structural motif at C terminal end. That is why both share common function.

b. Cdk8 is called as inhibitory module because Cdk8 show association with mediator complex and have inhibitory effect on the transcription proteins by phosphorylating them. Sometimes phosphorylation, increases the activity of transcription factors.

c. As, there is a existence of many phosphorylation sites in the CTD , presence of multiple CTD, the extent and pattern phosphorylation of CTD can be moderated to develop vast phospho-epitope

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