Learning objectives for this problem are to: Model how enzyme activities can shi

Question

Learning objectives for this problem are to: Model how enzyme activities can shift the state of chromatin in the genome .Use critical thinking and hypothesize how epigenetic mechanisms can cause cancer euchromatin heterochromatin ON Acetylated Histones OFF Methylated cytosine It was discovered that a patient with lung cancer was found to respond well to a new class of drug called DNA methyl transferase inhibitors (DNA methyl transferase is an enzyme that can add methyl groups to the cytosine bases in DNA) A) (5 points) As the patients doctor it is your job to explain to the patient why this new drug works so well for his specific kind of cancer. Oncogenes cause cell proliferation, while tumor suppressor genes stop cancer growth and even kill cancerous cells. Explain to the patient the probable cause of his cancer in terms of oncogene activity, or tumor suppressor gene activity, based on the success of this new drug. B) (5 points) The patient mentions that he has heard about another new drug called Histone Deacetylase (HDAC) Inhibitors. He wants to try those too. As his doctor what do you recommend? Explain your reasoning C) (5 points) A revolutionary genome editing tool, CRISPR, is now becoming useful to correct DNA sequences in the genome. Assuming this is a reliable method, would you recommend that this patient use CRISPR to correct his gene? Explain your reasoning.

Explanation / Answer

DNA methylation is the addition of methyl group to the DNA which makes it not accessible to transcription factors to initiate transcription. DNA acetylation is the transfer of acetyl group to lysine residues of histone protein and it makes the DNA to become accessible to transcription factor because it is relaxed state or euchromatin structure. DNA deacetylation removes acetyl group thus reducing positive charge and the DNA (negative charge) and lysine residues (positive) of histone make electrostatic interaction to form heterochromatin or condensed state.

Tumor suppressor genes code for proteins which regulate the cell cycle and prevent the progression to cancer. Proto-oncogenes are normal genes which codes for normal cell proteins but when there is mutation in such genes, it become oncogenes. Oncogenes codes for altered proteins which leads to uncontrolled cell proliferation or cancer.

A) The main cause of lung cancer is deactivation of tumor suppressor genes. So, when DNA methylation is prevented which makes tumor suppressor gene not accessible for transcription, the lung cancer be treated. Therefore, DNA methyl transferase inhibitors is given for lung cancer and it prevented DNA methylation and the tumor suppressor gene is then activated to code for proteins that regulate uncontrolled cell growth or proliferation.

B) Histone deacetylase inhibitor is not recommended because it would always make the DNA accessible to all types of transcription and it can lead to uncontrolled cell growth. And, it is the problem with DNA methyl transferase which acts in uncontrolled way to prevent transcription of tumor suppressor gene.

C) It is not recommended as CRISPR is gene editing tool which is basically used in lab experiments for various research activities. It is not yet successfully used to treat cancer patients and it is at the trial stage.

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