Exceptions from the Central Dogma

Question 1

Describe exceptions to the Central Dogma of molecular biology.

Answer 1

The Central Dogma outlines the flow of genetic information: DNA → RNA → Protein. Exceptions include reverse transcription (RNA → DNA), as seen in retroviruses, RNA viruses that replicate without DNA intermediates, and prions, where proteins propagate structural information without nucleic acids​
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Question 2

What is reverse transcription and which enzyme catalyzes it?

Answer 2

Reverse transcription is the process where RNA serves as a template to synthesize DNA. This is catalyzed by the enzyme reverse transcriptase, which has DNA polymerase and RNase H activities​
. Retroviruses like HIV use reverse transcription to integrate into the host genome.

Question 3

How does the mechanism of reverse transcription occur in retroviruses?

Answer 3

Reverse transcription begins when a retrovirus-specific tRNA hybridizes with the primer-binding site (PBS) on viral RNA. DNA is synthesized, RNA is degraded by RNase H, and two strand transfer or “jump” events occur to complete the synthesis of double-stranded viral DNA​
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Question 4

Why is reverse transcriptase a target for antiviral therapies?

Answer 4

Reverse transcriptase lacks proofreading ability, leading to high mutation rates. Drugs like AZT inhibit reverse transcriptase by mimicking nucleotides and preventing viral DNA synthesis, making it an effective strategy for treating HIV​

Question 5

What are prions, and how do they propagate without nucleic acids?

Answer 5

Prions are misfolded proteins that cause normal proteins to misfold into pathogenic forms. They bypass nucleic acid intermediates, violating the Central Dogma. Prions are responsible for diseases such as Creutzfeldt-Jakob Disease and mad cow disease​

Question 6

What is epigenetics and how does it differ from genetic mutations?

Answer 6

Epigenetics refers to heritable changes in gene expression that do not involve alterations in the DNA sequence​
. Unlike mutations, epigenetic modifications like DNA methylation and histone modification are reversible and influenced by environmental factors​
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Question 7

Explain the role of DNA methylation in gene regulation.

Answer 7

DNA methylation, particularly at CpG islands near promoters, adds methyl groups to cytosine residues, silencing genes by preventing transcription factor binding or recruiting proteins that compact chromatin​
. Methylation is crucial for normal development and cancer prevention.

Question 8

How can environmental factors influence epigenetics?

Answer 8

Factors like diet, toxins, and stress can lead to epigenetic changes. For example, royal jelly fed to bee larvae silences DNA methyltransferase (Dnmt3), allowing expression of genes that turn larvae into queen bees​
. Similarly, bisphenol A (BPA) exposure in mice reduces DNA methylation and affects phenotype​
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Question 9

What is the significance of epigenetic inheritance?

Answer 9

Epigenetic marks like DNA methylation can be passed through cell divisions and even generations, allowing organisms to “remember” environmental exposures or developmental cues without changing the DNA sequence​
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Question 10

How is epigenetics related to cancer?

Answer 10

In cancer, tumor suppressor genes are often silenced through promoter hypermethylation rather than mutation​
. This epigenetic inactivation can contribute to uncontrolled cell growth. Diet and bioactive compounds can influence epigenetic patterns, offering potential cancer prevention strategies​
.