Gene regulation

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Gene regulation

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USMLE® Step 1 style questions USMLE

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A biologist is conducting a study on gene expression using human cancer cells cultured in vitro. A modification affecting the expression of the TP53 gene is made, which leads to increased gene expression and increased production of the p53 protein. Which of the following best characterizes the most likely modification to these cancer cells?  

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Our DNA is like a library - found in the nucleus of our cells - with thousands of books.

Some of these books - called genes - are extremely important, because they carry the recipes for every single protein found in the cell.

Some of these proteins are necessary in all the cells - like the cytoskeletal proteins.

But other proteins, like neurotransmitters, are necessary only in certain cell types - like neurons.

Gene regulation is what allows the right cells to make the right proteins at the right time.

Now, on the molecular level, DNA is made up of two strands of nucleotides, so each gene is just a segment of this nucleotide sequence.

And there are four types of nucleotides: adenine, guanine, thymine, and cytosine - or A, G, T, C.

Now, the entire DNA molecule is wrapped around structural proteins called histones that package the DNA into nucleosomes - like when we roll yarn into a ball to keep it compact and organized.

Altogether, the entire yarn with the DNA plus the histones - is called chromatin.

The process of decoding the information stored in the DNA is called gene expression - and it includes transcription and translation.

Transcription is where the enzyme RNA polymerase uses the gene as a template to create a molecule that can leave the nucleus.

This molecule is called messenger RNA or mRNA and it has the same nucleotide sequence as the gene, with one tweak: it has uracil nucleotides - or U - instead of thymine.

This message is encoded so that any 3 nucleotide equate a specific codon which codes for an amino acid or is a stop codon which means that the protein is complete.

In translation, specialized proteins in the cytoplasm - called ribosomes - use the mRNA template to create a string of amino acids that make up the protein.

Gene regulation can occur at the level of transcription, post-transcriptional which is between transcription and translation, or translation.

Let’s start with transcriptional regulation - and to understand that let’s start with a deeper dive into transcription.

Transcription begins with general transcription factors binding to a unique DNA sequence – called the promoter – just upstream from a gene.

General transcription factors help unwind the DNA helix so that RNA polymerase can transcribe the gene.

However, general transcription factors can only bind to the promoter sequence if the DNA is not too tightly packed around the histones.

Usually, genes that the cell uses frequently - like the hemoglobin genes in red blood cells - are packed more loosely and therefore easier to access.

Summary

Gene regulation is the process by which a gene's expression is controlled. This control may be either activation or inhibition. Activational gene control occurs when a particular gene is turned on in response to some signal or stimulus. For example, genes that code for insulin production necessary for the body to metabolize sugar will be active (or "turned on") only when blood sugar levels are high.

Inhibitational gene control, on the other hand, happens when a particular gene is turned off in response to some signal or stimulus. For example, genes that code for insulin production will be inactive when blood sugar levels are low.