DLA-factors That Disrupt Transcription

Question 1

What is the clinical use of Rifampin/Rifampicin?

Answer 1

• an antibiotic from a strain of Streptomyces
• inhibits initiation of transcription
• blocks formation of the first phosphodiester bond by binding to prokaryote RNA polymerase
• RNA polymerase of eukaryotes is not affected
• used in treatment of tuberculosis

Question 2

What can cause Rifampin/Rifampicin resistance?

Answer 2

Mutations in the genes encoding the target proteins such as RNA polymerase and topoisomerases can lead to drug resistance

Question 3

How does the mushroom phalloides toxin work?

Answer 3

The mushroom Amanita phalloides (the death cap mushroom) produces a toxin called alpha-amanitin which is a potent inhibitor of RNA polymerase II

The microfilament toxin, phalloidin, that is also found in this mushroom is often erroneously citied for its toxicity. Phalloidin is not absorbed by the GI tract and does not contribute to toxicity by oral intake

Question 4

What are the clinical phases of Amanita phalloides poisoning?

Answer 4

1. Asymptomatic phase
2. Gastrointestinal phase (1-2 days)- severe diahrrea and vomitting
3. Apparent recovery phase - few symptoms
4. Hepatic phase- renal and liver failure

Death may occur in 7-10 days

Question 5

What is the treatment for phalloidin poisoning?

Answer 5

• gastrointestinal decontamination
• high dose penicillin (inhibits Amanitin act8vity in liver)
• liver transplant

Question 6

What is the function of antinomycin D?

Answer 6

Intercalating inhibitors of RNA synthesis

• binds tightly to double stranded DNA
• inhibits transcription and replication in both prokaryotes and eukaryotes
• primarily used as an anti-cancer drug (inhibiting DNA replication and cell division )
• not normally used as an antibiotic

Question 7

Transcription results in ______ Supercoils in front of RNA polymerase and __________supercoils behind the RNA polymerase

Answer 7

Positive

Negative

Question 8

What are the functions of the topoisomerases?

Answer 8

Gyrase- (another topoisomerase) introduces -ve supercoils

Topoisomerase I- relaxes -ve supercoils

Question 9

Why are topoisomerases needed?

Answer 9

In replication and transcription Supercoiling is generated.

This can cause the process to halt