Try it
Biochemistry · Epigenetics: DNA methylation and azacitidine
Sample itemA 72-year-old man with myelodysplastic syndrome is given azacitidine, a hypomethylating agent. Which principle explains why it can be effective?
Original practice item, not a recalled exam question. Nothing here is recorded.
The answer and the reasoning
B. It inhibits DNA methyltransferase, reversing promoter CpG methylation that silences tumour suppressor genes
Methylation of cytosine in CpG islands at promoters recruits proteins that compact chromatin and repress transcription. In myelodysplastic syndrome, tumour suppressor genes are often silenced this way. Azacitidine and decitabine are cytosine analogues incorporated into DNA that trap DNA methyltransferase, so methylation falls and gene expression can resume.
Option by option
A. It inhibits thymidylate synthase and starves cells of thymidine
Thymidylate synthase inhibition is the action of fluorouracil, and is not how azacitidine works.
B. It inhibits DNA methyltransferase, reversing promoter CpG methylation that silences tumour suppressor genes (correct)
Trapping DNA methyltransferase leads to demethylation and gene reactivation.
C. It intercalates into DNA and blocks topoisomerase II
Topoisomerase II inhibition is the action of agents such as etoposide and anthracyclines.
D. It inhibits histone deacetylase and compacts chromatin
Histone deacetylase inhibition is the action of vorinostat and does not describe azacitidine.
Source note: Original NextPrep sample item — pending expert review. This item is original practice material awaiting independent expert review, so confirm important facts in a standard textbook.
More Biochemistry questions
- Nucleotide metabolismA 4-year-old boy has intellectual disability, dystonia, self-mutilation and hyperuricaem…
- VitaminsA patient with megaloblastic anaemia and mild neurological signs has raised serum methyl…
- Amino acid metabolismA baby has a mousy odour, fair skin and developmental delay. Which enzyme is deficient?
- Glycogen storage diseasesA child has severe fasting hypoglycaemia, hepatomegaly, lactic acidosis and hyperuricaem…