What are transcriptional inhibitors?

What are transcriptional inhibitors?

Transcriptional inhibitors (TI) are drugs that inhibit global transcription by different mechanisms and usually induce programmed cell death. Some of these drugs, such as, seliciclib (R-roscovitine) and flavopiridol are currently in clinical trials against different types of cancer [1], [2], [3].

What makes up the transcription initiation complex?

Together, the transcription factors and RNA polymerase form a complex called the transcription initiation complex.

Do all Mrna have poly A tail?

mRNAs that are not exported are degraded by the exosome. Poly(A)-binding protein also can bind to, and thus recruit, several proteins that affect translation, one of these is initiation factor-4G, which in turn recruits the 40S ribosomal subunit. However, a poly(A) tail is not required for the translation of all mRNAs.

What are the inhibitors of DNA replication?

Quinolones are a key group of antibiotics that interfere with DNA synthesis by inhibiting topoisomerase, most frequently topoisomerase II (DNA gyrase), an enzyme involved in DNA replication.

What are the inhibitors of eukaryotic transcription?

To conclude, the classical inhibitors of transcription have advantages and drawbacks. Amanitin is highly selective for RNAP II and RNAP III but slow, actinomycin D is fast but its selectivity is poor, CDK9 inhibitors are fast and reversible but many genes escape transcription inhibition.

What is the purpose of 5 cap and poly-A tail?

5′ cap and poly-A tail Both the cap and the tail protect the transcript and help it get exported from the nucleus and translated on the ribosomes (protein-making “machines”) found in the cytosol 1start superscript, 1, end superscript. The 5′ cap is added to the first nucleotide in the transcript during transcription.

Why is A poly-A tail important?

The polyA tail makes the RNA molecule more stable and prevents its degradation and allows the mature mRNA molecule to be exported from the nucleus and translated into a protein by ribosomes in the cytoplasm.

Which drugs inhibit DNA polymerase?

The most frequently used drugs in this class include abacavir (90), emtricitabine (91), lamivudine (LAM) (92), and tenofovir (TFV). For each, the active metabolite can inhibit RT by incorporation into viral DNA, causing a termination of DNA chain elongation.

What antibiotic inhibits DNA synthesis?

Betalactam antibiotics (BLA) are the most widely used antibacterial drugs in practical medicine. Recent experiments suggested that BLA, especially after “aging” in aqueous solutions, have an inhibitory effect on the growth of a variety of cultured human cells by interfering with DNA synthesis (Neftel et al. Cell Biol.

What inhibits eukaryotic translation?

Among the known inhibitors of eukaryotic translation is cycloheximide (CHX, 1), the most common laboratory reagent used to inhibit protein synthesis (Fig. 1). CHX has been shown to block the elongation phase of eukaryotic translation.

What are three important functions of the 5 cap and poly A tail?

The 5′ cap protests the newly-synthesized mRNA from degradation. It also assists in ribosome binding to help initiating translation. 3′ poly-A tail protects mRNA from degradation, aids in exporting the mature mRNA to the cytoplasm, and is also involved in binding proteins to initiate translation.

Why is capping and tailing done?

This process is known as the capping of the mRNA. At the 3′ end of the mRNA, there is an addition of a chain of adenine nucleotides. This is known as the poly-A tail or the tailing mechanism. These are the modifications to protect the mRNA from degradation by nucleases.

What does the polyA tail do on mRNA?

The poly-A tail makes the RNA molecule more stable and prevents its degradation. Additionally, the poly-A tail allows the mature messenger RNA molecule to be exported from the nucleus and translated into a protein by ribosomes in the cytoplasm.

Which drug is inhibitor of DNA virus?

The guanosine depicted in this specific image is used for RNA synthesis but acyclovir inhibits the synthesis of DNA synthesis. One of the most often used antiviral drugs that works with the described mechanism is acyclovir (aciclovir), a guanosine analogue.

Which antibiotic inhibits DNA synthesis?

Can DNA-PK inhibition be improved by small molecule inhibitors?

In conclusion DNA-PK inhibition using small molecule inhibitors holds promise for improving cancer therapy. However, molecules currently known to specifically inhibit DNA-PK are limited by poor pharmacokinetics: metabolic lability leads to a short serum half-life.

What is an inhibitor of DNA binding?

Inhibitor of DNA binding (ID) proteins are a class of helix-loop-helix (HLH) transcription regulatory factors that act as dominant-negative antagonists of other basic HLH proteins through the formation of non-functional heterodimers.

What are the small molecule inhibitors of DNA PK?

Small molecule inhibitors of DNA-PK: (A) wortmannin, (B) LY294002 derivatives, and (C) other molecules with demonstrated inhibitory activity. One of the first identified inhibitors, wortmannin (1), a furanosteroid metabolite of the fungi Penicillium funiculosum, has been used experimentally to inhibit DNA-PK.

Are DNA-dependent protein kinase inhibitors a drug candidate for cancer?

Kashishian A., Douangpanya H., Clark D., Schlachter S. T., Eary C. T., Schiro J. G., et al. (2003). DNA-dependent protein kinase inhibitors as drug candidates for the treatment of cancer. Mol.