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Ch. 11 - DNA Replication and Recombination
Chapter 11, Problem 21

While many commonly used antibiotics interfere with protein synthesis or cell wall formation, clorobiocin, one of several antibiotics in the aminocoumarin class, inhibits the activity of bacterial DNA gyrase. Similar drugs have been tested as treatments for human cancer. How might such drugs be effective against bacteria as well as cancer?

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1
Understand the role of DNA gyrase: DNA gyrase is an enzyme that relieves the strain while double-stranded DNA is being unwound by helicase. It is crucial for DNA replication and transcription in bacteria.
Recognize the mechanism of clorobiocin: Clorobiocin inhibits DNA gyrase, preventing the bacteria from replicating their DNA, which ultimately leads to bacterial cell death.
Consider the similarity in target: Cancer cells, like bacterial cells, require rapid DNA replication for their uncontrolled growth. Drugs that inhibit DNA replication can potentially slow down or stop cancer cell proliferation.
Explore the concept of topoisomerases: In humans, topoisomerases are enzymes similar to DNA gyrase that manage DNA supercoiling and untangling during replication. Inhibiting these can disrupt cancer cell division.
Connect the dots: By targeting enzymes involved in DNA replication, such drugs can be effective against both bacteria and cancer cells, as both rely on these processes for growth and survival.

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Key Concepts

Here are the essential concepts you must grasp in order to answer the question correctly.

DNA Gyrase

DNA gyrase is an essential enzyme in bacteria that introduces negative supercoils into DNA, which is crucial for DNA replication and transcription. By inhibiting this enzyme, antibiotics like clorobiocin disrupt the normal functioning of bacterial DNA, leading to cell death. Understanding this mechanism is key to grasping how certain antibiotics can target bacterial cells specifically.
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Mechanism of Action of Antibiotics

Antibiotics work by targeting specific bacterial processes, such as protein synthesis, cell wall formation, or DNA replication. Clorobiocin's unique action on DNA gyrase exemplifies how different antibiotics can exploit bacterial vulnerabilities. This concept is vital for understanding why some antibiotics can be effective against both bacteria and cancer cells, as they may share similar cellular processes.
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Cancer Cell Biology

Cancer cells often exhibit uncontrolled growth and division, similar to bacterial cells. Many cancer treatments aim to disrupt the processes that allow these cells to proliferate. Since some antibiotics target mechanisms like DNA replication, they can also affect cancer cells, which rely on these processes for their rapid growth, making them potential candidates for cancer therapy.
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Related Practice
Textbook Question
Several temperature-sensitive mutant strains of E. coli display the following characteristics. Predict what enzyme or function is being affected by each mutation. No initiation occurs.
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Textbook Question
Several temperature-sensitive mutant strains of E. coli display the following characteristics. Predict what enzyme or function is being affected by each mutation. Synthesis is very slow.
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Textbook Question
Several temperature-sensitive mutant strains of E. coli display the following characteristics. Predict what enzyme or function is being affected by each mutation. Supercoiled strands remain after replication, which is never completed.
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Textbook Question
In 1994, telomerase activity was discovered in human cancer cell lines. Although telomerase is not active in most human adult cells, all cells do contain the genes for telomerase proteins and telomerase RNA. Since inappropriate activation of telomerase may contribute to cancer, why do you think the genes coding for this enzyme have been maintained in the human genome throughout evolution? Are there any types of human body cells where telomerase activation would be advantageous or even necessary? Explain.
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Textbook Question
The genome of D. melanogaster consists of approximately 1.7x10⁸ base pairs. DNA synthesis occurs at a rate of 30 base pairs per second. In the early embryo, the entire genome is replicated in five minutes. How many bidirectional origins of synthesis are required to accomplish this feat?
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Textbook Question
Assume a hypothetical organism in which DNA replication is conservative. Design an experiment similar to that of Taylor, Woods, and Hughes that will unequivocally establish this fact. Using the format established in Figure 11.5, draw sister chromatids and illustrate the expected results establishing this mode of replication.
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