DNA supercoiling is a process to make DNA fit inside the cell nucleus and regulates transcriptional activities. But do you know it performs 5 other functions for a cell too?
DNA is a type of nucleic acid present in a cell with either linear or circular topology. Smaller DNA like the bacterial plasmids are circular in nature and freely floating while eukaryotes have complex “unorganized” and a larger DNA molecule.
DNA is very large in length, as per the BBC Science Focus Magazine, “the DNA is approximately 2 meters in length” which is probably more than a thousand times the size of a cell.
So it is difficult for longer DNA to fit in a cell nuclease, but a process known as supercoiling helps cells to organize their DNA. Hence the pivotal function the DNA supercoiling has is to make DNA fit in the cell. But there are other functions it performs as well.
What are those? Let’s find out.
What is DNA supercoiling?
In a layman, DNA supercoiling has been known as a process of DNA winding or packaging in a cell.
DNA supercoiling is a higher-order organization of DNA which is known as DNA packaging. It allows the winding and interwinding of DNA on and with one another. This process has many important functions.
Two types of DNA supercoiling processes are positive supercoiling and negative supercoiling. The positive supercoiling occurs when DNA supercoils in a clockwise manner in right-handed DNA.
Negative supercoiling occurs when DNA supercoils in an anticlockwise manner in left-handed DNA. Note that only the dsDNA supports supercoiling.
Supercoiling is a topological feature of the DNA and the amount of coiling, supercoiling, twisting and writhing can be calculated by mathematical equations. The unit of supercoiling is referred to as a linking number- a topological feature of DNA.
Now let us see what are the different functions the supercoiling performs for a cell.
5 Important functions DNA supercoiling performs:
Allow DNA to fit in a cell:
As aforementioned, the stretched DNA of a single cell is 2 mt long. Means, it should be highly organized to fit in a cell. DNA supercoiling allows the entire genome to shrink and settle in the cell nucleus.
Supercoiling of DNA which is the coiling of single-stranded DNA with one another and supercoiling of duplex DNA on one another facilitates DNA packaging. Technically, the interaction of DNA with certain proteins forces it to supercoil by interaction.
But as highly supercoiled DNA reduces the rate of replication, enzymes such as DNA topoisomerase and gyrase regulate the process of winding. If you wish to understand how topoisomerases work, you can read this article:
Particularly, various histones are one among the class of those proteins which interact with the DNA and force the supercoiling of DNA. The entire genomic DNA of a cell fits in a cell through this process. Note that histones are structural units of chromosomes.
Do you know?
Studying the interaction between protein and DNA is known as DNA footprinting which provides information on how DNA interacts with protein, how much DNA is involved in it and what are the consequences. If you wish you can learn more here: What is DNA footprinting?- Principle, Steps, Process and Applications.
Provides stability to DNA:
The stability of DNA is very important for a cell to perform various metabolic activities. Single-stranded and unwind DNA certainly are unstable and can interact wrongly. Unstable DNA also disrupts the process of DNA packaging in eukaryotes too.
On the other hand, supercoiled DNA is highly stable. Through correct base-pairing, the helix of dsDNA stables while through supercoiling of dsDNA duplex, the entire genome becomes stable in a cell.
However, to allow various enzymatic reactions, it becomes unstable, but the stability of DNA is important to form the structure like a chromosome. The process of stabilizing and destabilizing the DNA by supercoiling and unwinding controls the process of gene expression and replication.
Prevent unnecessary enzymatic reactions:
Relaxed DNA is susceptible to enzymatic reactions. Besides, DNA as a “gene”; regulatory DNA sequences, which are usually non-coding, work as marker regions for enzymatic binding as well as catalytic actions.
Enzymes involved in replication, transcription and translations (which is the process of central dogma) use regulatory elements to settle on a DNA for catalytic activity. This literally indicates that unpacked DNA leads to uncontrolled DNA metabolic activities.
DNA supercoiling thereby doesn’t allow enzymes to work by blocking regulatory regions and only allows when needed.
This process is automatically controlled and highly tissue-specific.
Control gene expression:
One of the crucial functions the DNA supercoiling has is maintaining the gene expression profile. Note first that uncontrolled gene expression, either over or underexpression causes various problems for a cell and the organism. It results in developmental, mental or physical abnormalities.
As aforementioned, supercoiling controls the process by allowing and disallowing enzymes during gene expression. Supercoiling and uncoiling simultaneously block and allow regulatory elements to interact with proteins involved in gene expression.
When DNA gets supercoiled, as we discussed above, proteins like histones interact with DNA and block sites for other enzymes to work.
Heterochromatin regions of the DNA are highly packed (supercoiled) and thus are transcriptionally inactive and remain unexpressed. By this means, supercoiling regulates the transcriptional activities of a cell.
Forms chromatin, chromatids and chromosomes:
Chromosomes are the highly-organized, structured and higher-ordered structure of DNA. It is formed by the interaction between proteins and DNA. Again, various types of histones like H1, H2A, H2B, H3 and H4 bind with different DNA regions and form lower to higher-ordered structures like nucleosome, bead-on-a-string, chromatin, 30 nm fiber, chromatids and chromosomes. See this image,
The chromosome is a final product of DNA packaging by supercoiling having two chromatids, arms and centromeres. 23 pairs of chromosomes a typical cell has, except germ cells.
The structure “chromosome” eventually helps DNA to fit in a cell and inheritance of genes from one to another cell.
Supercoiling is an important topological characteristic of DNA and a “must-required” process. Practically, the supercoiled DNA migrates faster in a gel but as it is huge, it can’t run faster than linear or circular DNA.
Supercoiling and other properties of DNA topology can be studied by mathematical models and equations. You can read about it by clicking the link given in this article, somewhere.
An external article relevant to the present article: Role of DNA supercoiling during transcription. (Ma, J., & Wang, M. D. (2016). DNA supercoiling during transcription. Biophysical reviews, 8(Suppl 1), 75–87. https://doi.org/10.1007/s12551-016-0215-9).