Lecture Inhibitors of Transcription notes.pdf

Lecture Inhibitors of Transcription notes

1. Inhibitors of Transcription
Dr. ManikandanKathirvelM.Sc., Ph.D., (NET)
Assistant Professor,
Department of Life Sciences,
KristuJayantiCollege (Autonomous),
Reaccredited with "A++" Grade by NAAC
K. Narayanapura, Kothanur(PO)
Bengaluru560077
Mobile: [phone]
Email:[email protected]
ORCID ID: 0000000270066334

2. Transcription
•The process by which RNA is produced from the part of DNA for the expression of
gene
•This step is the 1
st
step for the gene expression.
•In Prokaryotes, Transcription occurs in cytoplasm and in eukaryotes it occurs in
nucleus
•Steps
I.Initiation
II.Elongation
III.Termination
•Major enzymes involved
a.DNA Helicase
b.RNA Polymerase

4. Inhibitors
•Any molecules which can inhibit the role of RNA Polymerase can block the
activity of Transcription.
•There are both gene specific and non gene specific inhibitors.
•Mostly the inhibitors are Antibiotics used against bacterial pathogens, Antifungal
for Eukaryotes.
•Histone methylation also acts as Inhibitors for transcription.
•They inhibit the action of RNA polymerase, DNA helicase, DNA topoisomerase
by binding to it or by producing free radicals which can inhibit transcription.
•There are 2 types of inhibitors
a.Type 1: Inhibitors interact with DNA dependent RNA polymerase and inhibit the RNA
synthesis.
b.Type 2: Inhibitors interact with DNA(Deoxyribonucleic acid) and inhibit the RNA
synthesis.

5. •Type 1: Inhibitors interact with DNA dependent RNA polymerase and
inhibit the RNA synthesis.
The enzyme which transcribe DNA synthesizing RNA(DNA dependent
RNA polymerase) have structural differences in eukaryotic and prokaryotic cells.
In Prokaryotic cells(Streptolydiginand Rifamycin) and In Eukaryotic cells
(α-amanitin)
•Type 2: Inhibitors interact with DNA(Deoxyribonucleic acid) and inhibit
the RNA synthesis.
The antibiotics interact with DNA and inhibit the RNA synthesis.
ActinomycinD, ChromomycinA3, MithramycinA

7. Rifamycin–(C43H58N4O12)
•Rifamycin–antibacterial drug used to treat tuberculosis and leprosy.
•Rifamycinbinds to the beta subunit of Prokaryotic RNA polymerase
•This acts as the inhibitor of transcription at initial stage
•It is a bacterial transcription inhibitors and doesn’t work on eukaryotes
•Synthesized either naturally by the organism Amycolatopsis
rifamycinicaor artificially.
•Subclass of the larger family of ansamycins

8. α–amanitin–(C39H54N10O14S)
•α–amanitinis a molecule which made from the death cap mushroom which acts as
the potent inhibitors of RNA polymerase.
•α–amanitincan inhibit RNA polymerase II activity in both initiation and elongation
stages.
•It is a toxin produced by Amanita phalloides(Mushroom) which inhibits the mRNA
synthesis.
•α-amanitininteracts with bridge helix in RNA polymerase II.
•The addition of α-amanitincan reduce the rate of RNA polymerase2, Transcribing
on DNA from several thousands to few nucleotides per minute.
•Binding of α-amanitinputs a constraint on its mobility, hence slowing down the
translocation of the polymerase and the rate of synthesis of the RNA molecule

9. ActinomycinD–(C64H86N12O16)
•It is a class of polypeptide antitumor antibiotics isolated from soil
bacteria of the genus Streptomyces.
•It contains two cyclic peptides bound to the chromophoric
phenoxazonering.
•It binds specifically to the minor groove of the DNA double helix, and
thus prevents it from being a template for RNA synthesis.
•Its ability to inhibit growth of rapid dividing cells makes it a effective
agent in cancer treatment.