Question

Retroviruses, like HIV which causes AIDS, have their genetic information in the form of RNA. Reverse transcriptase synthesizes a DNA copy of the viral genome. One drug used in treating AIDS is AZT, an analog of deoxythymidine, which has an azido group at the \(3^{\prime}\) position of the sugar. It can be phosphorylated and competes with dTTP for incorporation into the reverse transcript. Once incorporated, its presence terminates chain elongation. The growing chain is terminated becausc A. the analog can not hydrogen bond to RNA. B. the presence of the AZT analog inhibits the proofreading ability of reverse transcriptase. C. AZT does not have a free \(3^{\prime}\) - \(\mathrm{OH}\). D. the analog causes distortion of the growing chain, inhibiting reverse transcriptase. E. \(d T T P\) can no longer be added to the growing chain.

Short answer

Answer: The primary reason for the termination of the growing chain is that AZT does not have a free \(3^{\prime}\) - \(\mathrm{OH}\) group. This prevents the formation of phosphodiester bonds with the next incoming nucleotides and ultimately terminates the growing chain.

Step-by-step solution

Understanding the action of AZT in the RNA replication process

AZT is an analog of deoxythymidine that can be phosphorylated and competes with dTTP for incorporation into the reverse transcript. Once incorporated, it causes the termination of the growing chain. Now, we will go through each option to identify the accurate reason behind the termination.

Evaluating Option A

Option A states that the analog cannot hydrogen bond to RNA. This statement is not accurate, as AZT can form hydrogen bonds in the same way that deoxythymidine does with the RNA. So, this option is incorrect.

Evaluating Option B

Option B suggests that the presence of the AZT analog inhibits the proofreading ability of reverse transcriptase. Although AZT can affect the process of reverse transcription, it does not specifically inhibit the proofreading ability of reverse transcriptase. So, this option is also incorrect.

Evaluating Option C

Option C mentions that AZT does not have a free \(3^{\prime}\)-\(\mathrm{OH}\). This statement is correct. The azido group present at the \(3^{\prime}\) position of AZT replaces the hydroxyl group (\(\mathrm{OH}\)) necessary for forming a phosphodiester bond with the next incoming nucleotide. As a result, the incorporation of AZT causes chain termination. Therefore, this option is the correct answer.

Evaluating Option D

Option D states that the analog causes distortion of the growing chain, inhibiting reverse transcriptase. Although this may seem like a plausible cause, the termination of the chain is primarily due to the azido group at the \(3^{\prime}\) position, not because it causes distortion. So, this option is incorrect.

Evaluating Option E

Option E says that dTTP can no longer be added to the growing chain. While this is true that the incorporation of AZT prevents further addition of dTTP, it doesn't give the specific reason. The primary reason is the lack of a free \(3^{\prime}\)-\(\mathrm{OH}\) group in the AZT molecule, which is explained already in Option C. Therefore, this option is also incorrect.

Conclusion

The correct answer is Option C: AZT does not have a free \(3^{\prime}\) - \(\mathrm{OH}\). The chain termination occurs because AZT, once incorporated, does not allow the formation of phosphodiester bonds with the next incoming nucleotides as it lacks a free \(3^{\prime}\)-\(\mathrm{OH}\) group due to the presence of an azido group.