Molecular biology and genetics: zidovudine as a chain terminator: practice question

A Biochemistry question in the style of the NEET PG paper. Answer it first, then read why the right option is right and why each of the others is wrong.

Try it

Biochemistry · Molecular biology and genetics: zidovudine as a chain terminator

Sample item

Zidovudine is a nucleoside analogue used against HIV. Why does its incorporation by reverse transcriptase stop viral DNA synthesis?

AIt cross-links the two strands of the proviral DNA double helixBIt blocks RNase H cleavage of the RNA strand in the hybrid duplexCIt binds the integrase active site and prevents proviral integrationDIt lacks a free 3'-hydroxyl group, so the next nucleotide cannot be added

Original practice item, not a recalled exam question. Nothing here is recorded.

The answer and the reasoning

D. It lacks a free 3'-hydroxyl group, so the next nucleotide cannot be added

After phosphorylation to the triphosphate, zidovudine is incorporated into growing viral DNA by reverse transcriptase. It has an azido group in place of the 3'-hydroxyl, so no phosphodiester bond can form with the next nucleotide and chain elongation terminates. Dideoxynucleotides act the same way in Sanger sequencing.

Option by option

A. It cross-links the two strands of the proviral DNA double helix
Cross-linking of strands is the action of alkylating agents, not nucleoside analogues.
B. It blocks RNase H cleavage of the RNA strand in the hybrid duplex
RNase H inhibition is not the mechanism of zidovudine.
C. It binds the integrase active site and prevents proviral integration
Integrase inhibitors such as raltegravir act differently from nucleoside analogues.
D. It lacks a free 3'-hydroxyl group, so the next nucleotide cannot be added (correct)
Correct. The missing 3'-OH makes it an obligate chain terminator.

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.

Questions about this Biochemistry question

What is the answer to this Biochemistry question?

The best answer is D, It lacks a free 3'-hydroxyl group, so the next nucleotide cannot be added. After phosphorylation to the triphosphate, zidovudine is incorporated into growing viral DNA by reverse transcriptase.

Why is "It cross-links the two strands of the proviral DNA double helix" not the answer?

Cross-linking of strands is the action of alkylating agents, not nucleoside analogues.

Why is "It blocks RNase H cleavage of the RNA strand in the hybrid duplex" not the answer?

RNase H inhibition is not the mechanism of zidovudine.

Why is "It binds the integrase active site and prevents proviral integration" not the answer?

Integrase inhibitors such as raltegravir act differently from nucleoside analogues.

What concept does this question test?

It tests Molecular biology and genetics: zidovudine as a chain terminator in Biochemistry. It has an azido group in place of the 3'-hydroxyl, so no phosphodiester bond can form with the next nucleotide and chain elongation terminates. Dideoxynucleotides act the same way in Sanger sequencing.

How hard is this question?

We tag it as an application question: it asks you to use a fact on a patient or a finding. The tag is our own editorial judgement, not an official difficulty rating, so read the reason for every option, not only the answer.

How should I study Molecular biology and genetics: zidovudine as a chain terminator?

Build one table of enzyme deficiency, disease, inheritance and key finding, then revise it by spaced recall. Then use the flashcards and the other Biochemistry questions on this site to test what stuck.

Is this a real NEET PG question?

No. It is an original practice item (editorial status: sample, version 1). NextPrep does not publish recalled or leaked questions, and independent faculty review of this item has not been completed yet, so confirm important facts in a standard textbook.