Biology and Physical Factors #2: On and Off

DNA strands are long (several meters long). How on earth do they then fit inside the nucleus of a cell? By bending and folding themselves. But not in any random way. They wrap themselves around proteins 10 nanometers in size called histones. But it would require a lot of force to compress them like this. What is the source of that much force? The answer is electrostatic force, between the negatively charged DNA and the positively charged histone.

 

This isn’t just “intellectual curiosity”. Which parts of the DNA are “expressed” as proteins depends on the packaging and wrapping of the DNA. How? Remember DNA strands are read by a transcription molecule called RNA. Parts of the DNA that are inaccessible (due to the way they are wrapped) won’t be expressed. It has thus been turned “off”! Accessible = On; inaccessible = Off.

“The physical arrangement of DNA is a powerful tool for regulating the activities of the cell.”

writes Raghuveer Parthasarathy in So Simple a Beginning.

 

But this doesn’t explain how genes get turned On and Off dynamically. How do genes get (de)activated over time and based on triggers? To answer this, Parthasarathy asks us to imagine a simple bacterium.

 

This bacterium likes to eat sugars, and to digest them it needs to make the right proteins. But it wants to make those proteins only when it ingests sugar. How does it make that happen? Well, DNA has a gene (the part that is used to create a protein), but upstream from that, it has two opposing sites – promoter and repressor. As the names suggest, one is to activate the gene, the other to deactivate the gene. The green blob above all this is the RNA that is trying to read the gene. 


Back to our bacterium. The gene (blue) is the part that codes for the sugar digesting protein. The bacterium also codes for a protein (red blob) that binds to the repressor site. 

When this red blob is present and bound to the repressor site, the RNA reader (green blob) is physically obstructed from moving through the DNA to reach the gene (blue). If it can’t read the gene, the sugar digesting protein won’t be made.

 

That’s half the answer. What if there is sugar in the system? How does the bacterium now “decide” to make the digesting protein? The answer is very creative. When there is sugar (lactose), the bacterium creates something called allolactose using this lactose. This allolactose has great affinity to the repressor (red blob), so it goes and attaches itself to the repressor. In doing so, it bends the repressor (red blob).  With this distorted shape, the repressor can no longer bind to the DNA and thus gets detached from the DNA. With the repressor (red blob) gone, the RNA reader (green blob) can read the DNA all the way to the gene (blue) and create the protein needed to digest the sugar. 

Very ingenious.

 

This mechanism isn’t unique to this particular bacterium. Rather, this is one of the general principles by which genes are activated and deactivated – activate and repress via physical obstruction (or lack of it) based on the presence (or absence) of certain triggering molecules.

 

A physical mechanism is in play, which is the theme of the book.

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