In what form does cfDNA exist?

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Last time we saw that DNA is released into blood by cells. But in what form is it released?  We know that DNA remains stable inside the cell. But what happens to it when it comes out of the cell? Does it remain stable? Well, cell-free DNA is known to exist in many forms. 


Forms of cfDNA


Free DNA fragments

One is that of a free or unbound DNA fragment, that is, the DNA fragment by itself without being bound to any surface. But without being bound to anything, can DNA be stable in blood? A good question, as our blood is known to contain proteins that can destroy DNA, called as DNases. But some studies reported that the activity of DNases was low in some diseases. For example, Svetlana Tamkovich and their group,  in 2006, compared DNase activity with cell-free DNA concentration in cancer patients. They found that DNase activity was low in cancer patients, but high in normal people. This means that more amount of cell-free DNA can survive in the blood of cancer patients than in the blood of normal people. But how long does cell-free DNA stay in blood anyway? Some researchers studied just that, and they found that the half-life of cell-free DNA is less than two hours. 

Now, half-life means the time in which the amount of a thing reduces to half of its original quantity. For example, imagine that we drop a teaspoon of sugar into a glass of water, and we don't stir it. We simply wait and watch. Let's suppose that half teaspoon of sugar dissolves in the water within 5 minutes. So after 5 minutes, the amount of sugar is half of what was added to the glass at the beginning. That means that the half-life of 1 teaspoon sugar in water is 5 minutes. Now coming back to cell-free DNA, half of the amount of cell-free DNA is cleared away within 2 hours of being released from the cells. 

Now, if free DNA cannot remain stable in blood for long, that means, to last longer, it has to be protected somehow. How can it be protected?  Either it has to be bound to something or packed inside  something, so that DNases can't reach it. Such bound forms are described below.

Nucleosomes

Now, imagine that we have a long length of thread, say an embroidery thread of a rare color, that we want to store. How would we store it? We cannot keep it as it is, because it would get tangled and would occupy a lot of space. We want the thread to be safe, not get tangled and occupy less space. So what do we do? We wrap it around a spool. 

In the same way, DNA is a sort of very long thread. If we were to stretch out the DNA in just one cell, the length of this DNA would be about 2 m! All the DNA in all our cells put together could wrap twice around the entire Solar System! 

So how does all this DNA fit into such tiny cells? Like we saw above with the thread wrapped around a spool, DNA is wrapped around proteins called histone proteins. When wrapped around these histone proteins, the DNA looks like beads on a string. Each of these "beads" is a unit structure called as nucleosome. Nucleosomes are basic structural unit of DNA packaging. 

These nucleosomes can also be released by cells into blood.

Vesicles

 Vesicles are structures made of lipids that enclose liquid. They are generally used for secretion, uptake and transport of material within the cell. Vesicles include  apoptotic bodies, exosomes, and microparticles. Apoptotic bodies are formed when the cell undergoes apoptosis or programmed cell death. They contain fragments of the cell contents. Exosomes and microvesicles are smaller vesicles containing DNA, RNA or protein. They can transfer molecules from one cell to another. 

Virtosomes

Virtosomes are complexes of DNA, RNA, proteins and lipids. cfDNA can also be present attached to the cell surface or bound to serum proteins. 

So, these are the different forms in which cell-free DNA is present in the blood circulation. If you have any comments or queries, please post them in the Comments section below. In the next post, we will see how a cell releases cell-free DNA  into the blood. 


References

1. Wikipedia

2. https://www.sciencefocus.com/the-human-body/how-long-is-your-dna/

3. Aarthy et al (2015). Role of circulating cell-free DNA in cancers

Comments

  1. Winning habitsFebruary 12, 2021 at 6:45 AM

    Please explain the difference between cell free DNA and DNA

    ReplyDelete
    Replies
    1. BiobabblesFebruary 12, 2021 at 5:58 PM

      When a cell releases DNA into the blood, this DNA is called cell-free DNA, because it is out of the cell. Please also look at this post (https://liquidbiopsy.blogspot.com/2021/02/introduction-to-circulating-nucleic.html) to know about cell-free DNA

      Delete

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