How does cell-free DNA come into the blood? - Part 2

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 In the last post, we saw how cells release DNA actively. By actively, we mean that the cells put in effort to release the DNA for a purpose. Can cells also release DNA without any effort? Yes, of course, that is passive release of DNA. We saw one way of passive release last time and that is NETosis suicidal. To recap, NETosis is a process in which some types of WBCs release NETs to catch microbes. NET stands for neutrophil extracellular traps, a mixture of DNA and protein. This acts like a net to catch microbes like bacteria. We also learned that there two types of NETosis: vital and suicidal. In vital, the cell remains alive. But in NETosis suicidal, the cells burst to release the NETs or neutrophil extracellular traps. In fact, most processes of passive DNA release involve a form of cell death. Let's look at some of them. 

Passive cfDNA release


Apoptosis

Apoptosis is also known as programmed cell death. The apoptosis comes from Ancient Greek, meaning "falling off" of leaves from trees. It is usually used to get rid of unwanted cells in the body. An example of unwanted cells are those which are damaged beyond repair. It can also be very old cells that die to make way for the new. They trigger signals at the molecular level that start the apoptosis process. Now, we will look at the changes happening to the cell, that ultimately results in DNA being released into the blood. At the start of the apoptotic process, the cell starts shrinking.  Next, the coiled up DNA inside the nucleus (chromatin) starts condensing. Enzymes called nucleases cut up the DNA into fragments of different sizes. The cell membrane starts to fold in on itself. This folding creates protruding blisters on the cell surface called blebs. The blebs form around the cell organelles. This process is called blebbing. The nucleus breaks into fragments. The blebs break off from the cell, forming an apoptotic body. Look at this post for information about apoptotic bodies. In this way, the cell finally breaks into apoptotic bodies, each containing a part of the cell's content. The apoptotic bodies are then absorbed by neighboring cells or a type of immune cells called phagocytes. 

Necrosis

Necrosis is a more chaotic process. Imagine dropping an egg on the floor. It would make quite a mess, right? Necrosis acts in the same way. Necrosis is a form of premature cell death, that happens when a cell is injured or undergoes some trauma. Like apoptosis, there are signaling pathways that start necrosis, when the cell is injured. Blebs also form on the cell surface. But here, the membranes of the cell and its nucleus then break in many places. Because of this, the cell contents leak out into the surrounding. Apoptosis is a controlled process and can be beneficial. In contrast, necrosis is uncontrolled and can harm the surrounding tissue.

Oncosis and pyroptosis

Oncosis and pyroptosis are other forms of cell death which can release DNA. Oncosis is also known as ischemic cell death. Damage to the cell membrane causes ionic imbalance in the cell. This causes the cell to swell and eventually leads to cell death. Pyroptosis is a form of programmed cell death. It takes place when the cell is infected with pathogens like bacteria, fungi or viruses.

So these are some ways by which DNA reaches the bloodstream. If you have any comments or queries, please post them in the Comments section below! Good day!


Reference:

1. Kustanovich A, Schwartz R, Peretz T, Grinshpun A. Life and death of circulating cell-free DNA. Cancer biology & therapy. 2019 Aug 3;20(8):1057-67. 

2. Wikipedia

3. https://www.genome.gov/genetics-glossary/apoptosis#:~:text=Apoptosis%20is%20the%20process%20of,a%20role%20in%20preventing%20cancer.

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