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Review Question - QID 108463

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QID 108463 (Type "108463" in App Search)
A 62-year-old man with small cell lung cancer undergoes radiation therapy. His oncologist explains that radiation causes DNA damage and double-strand breaks, and this damage stops the cancer cells from growing because they can no longer replicate their DNA. One key mediator of this process is a cell cycle regulator called P53, which is upregulated after DNA damage and helps to trigger cell cycle arrest and apoptosis. One mechanism by which P53 activity is increased is a certain chromatin modification that loosens DNA coiling allowing for greater transcription of the proteins within that region of DNA. Which of the following enzymes most likely causes the chromatin modification described in this case?

DNA methyltransferase

10%

20/193

Histone acetyltransferase

60%

115/193

Histone deacetylase

16%

30/193

DNA topoisomerase

12%

24/193

Xist

1%

1/193

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The process described is most consistent with acetylation of histones leading to electrostatic repulsion from DNA and loosening of DNA packaging. This process increases the transcription of the genes located near the acetylated histones.

Chromatin consists of DNA packaged into nucleosomes along with a core histone octamer. These small, positively charged proteins attract negatively charged DNA allowing for 2 loops of DNA to wrap around each octamer. These DNA-histone interactions must be unwound for transcriptional machinery to efficiently activate DNA transcription so the state of chromatin packaging is important in protein expression levels. Methylation and acetylation of chromatin structures is the most well-characterized method of controlling the winding of DNA in nucleosomes. Uncharged modifications such as methylation make the DNA structure more compact and decrease transcription whereas charged modifications such as acetylation unwind the nucleosome structure and increase transcription. Transcriptionally repressed chromatin is called heterochromatin and is dense on microscopy. Transcriptionally active chromatin is called euchromatin and is diffuse on microscopy.

Incorrect Answers:
Answer 1: DNA methyltransferase is responsible for methylation of CpG islands within DNA. This serves the functions of repressing DNA transcription and distinguishing between old and new strands for mismatch repair purposes in prokaryotic organisms.

Answer 3: Histone deacetylase removes acetyl groups from histones leading to a less acetylated chromatin structure. This decreases the transcription of genes because nucleosome structure becomes more compact without the acetyl modifications.

Answer 4: DNA topoisomerases are enzymes that participate in the overwinding or underwinding of DNA. They are important for DNA replication and transcription but are not involved in heterochromatin-euchromatin transformation.

Answer 5: Xist is a gene responsible for random inactivation of one X chromosome in females through diffuse methylation. This inactivation leads to the production of "Barr bodies". X inactivation is randomly chosen by somatic cells leading to the phenomenon of mosaicism.

Bullet Summary:
Acetylation of chromatin causes unwinding and transcriptional activation, leading to a state known as euchromatin.

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