Question

Interfering with topoisomerases is one way of inhibiting DNA replication. Certain antibiotics target DNA gyrase (type II topoisomerase) of \(E\) coli inhibiting catalytic activity. Topoisomerase poisons prevent resealing of the phosphodiester bond, leaving covalent protein-DNA junctions. These compounds are used in rreating infections and as chemotherapeutic agentsAll of the following are correct about double-strand breaks in DNA except they A. can lead to loss of genetic information. B. are always involved in homologous recombination. C. are involved in nonhomologous recombination. D. are associated with a heterodimer (Ku) in mammals. E. can lead to mutations or improper regulation of gene expression.

Short answer

Answer: B. are always involved in homologous recombination.

Step-by-step solution

Understanding double-strand breaks

Double-strand breaks in DNA are instances where the phosphate backbone of both strands has been cleaved, leading to breaks in the continuity of the DNA. These breaks can have significant consequences, as they can disrupt genetic information and lead to mutations or improper regulation of gene expression.

Evaluating Option A

Option A states that double-strand breaks can lead to the loss of genetic information. This statement is correct, as during the repair process, genetic information may be lost or altered if the repair mechanism fails to correctly restore the original DNA sequence.

Evaluating Option B

Option B states that double-strand breaks are always involved in homologous recombination. This statement is not correct. While double-strand breaks can be involved in homologous recombination, they are not always a part of this process. Homologous recombination can also occur without double-strand breaks. Therefore, this statement is the answer.

Evaluating Option C

Option C states that double-strand breaks are involved in nonhomologous recombination. This statement is correct. Nonhomologous recombination is a type of DNA repair mechanism that involves the joining of broken DNA without the need for a homologous region for the repair. This process often involves double-strand breaks.

Evaluating Option D

Option D states that double-strand breaks are associated with a heterodimer (Ku) in mammals. This statement is correct. The Ku heterodimer is a protein complex that plays a critical role in nonhomologous end-joining, a DNA repair mechanism specifically involved in repairing double-strand breaks in mammals.

Evaluating Option E

Option E states that double-strand breaks can lead to mutations or improper regulation of gene expression. This statement is correct, as the loss or alteration of genetic information during the repair of double-strand breaks can lead to changes in the DNA sequence or gene expression.

Conclusion

The statement that is not correct about double-strand breaks in DNA is option B: "are always involved in homologous recombination."

Key concepts

DNA Replication Inhibition

DNA replication is a vital process for cell division, ensuring that genetic material is accurately duplicated. However, sometimes it's crucial to inhibit this replication, particularly during the treatment of infections or cancer. One method of inhibition involves interfering with topoisomerases, enzymes responsible for solving topological problems in DNA during replication.

One example is the antibiotic targeting of DNA gyrase, a type II topoisomerase in bacteria like E. coli. These antibiotics inhibit the catalytic activity, preventing DNA replication and thus bacteria proliferation. In humans, topoisomerase poisons that prevent the resealing of the phosphodiester bond, leaving covalent protein-DNA junctions, are used as chemotherapeutic agents. The interrupted DNA replication can lead to double-strand breaks, potentially resulting in cell death—a beneficial outcome in cancer therapy.

Homologous Recombination

Homologous recombination is one of the key DNA repair mechanisms that ensures genetic integrity. It involves the exchange of genetic material between two similar or identical DNA molecules. This process is crucial for the repair of double-strand breaks, especially during DNA replication when the sister chromatid is readily available as a template.

Homologous recombination relies on the sister chromatid to accurately repair the break, thereby preserving the genetic information. It is true that double-strand breaks can initiate homologous recombination, but they are not always involved. This is a precise and high-fidelity repair process, which is essential for maintaining genomic stability and preventing mutations.

Nonhomologous Recombination

Nonhomologous recombination, also known as nonhomologous end-joining (NHEJ), is another method for repairing double-strand breaks in DNA but differs from homologous recombination as it doesn't require a homologous sequence to guide the repair. In NHEJ, the broken ends of DNA are directly ligated without the need for a template.

In mammals, this quick-fix mechanism involves a protein complex known as Ku, which assists in the joining of the DNA ends. While NHEJ is efficient, it is also prone to errors, which can result in the loss or addition of nucleotides at the break site, potentially leading to mutations.

DNA Repair Mechanisms

All living organisms have evolved complex repair mechanisms to address various forms of DNA damage, one of the most severe being double-strand breaks. Effective DNA repair is crucial for cellular survival and prevention of diseases such as cancer.

Aside from homologous recombination and NHEJ, DNA repair includes base excision repair, nucleotide excision repair, and mismatch repair, among others. These mechanisms are tailored to different types of DNA damage and ensure the cell's genetic material is maintained with high fidelity. However, if these repair processes are compromised, it can result in mutations or improper gene expression, highlighting the importance of efficient and accurate DNA repair mechanisms.