Snapshot: What is Non-Homologous End Joining?

What is DNA damage?

As we go through life, our DNA undergoes a lot of stress, which can ultimately lead to DNA damage. The different stressors that can cause DNA damage are environmental factors such as UV light, radiation, and certain toxins. Additionally, DNA damage can be caused by metabolic processes that occur naturally in our body. DNA damage can manifest in multiple forms. One form of DNA damage are DNA breaks, which arise when either one or both of the DNA strands break, creating a physical separation between the DNA bases. Every day, each cell will experience about 50,000 single-stranded breaks, and every cell division will lead to about ten double-stranded breaks.

A blue DNA molecule that is broken in half, like it has been cut with a pair of scissors — An artist’s drawing of a double-stranded DNA break. Image part of the public domain.

How is the DNA repaired?

Thankfully, although DNA damage is a common occurrence in our cells, there are many ways our body can repair the damage. The type of repair is thereby determined by the type of DNA damage and the growth stage of the cell. A commonly used repair pathway to fix double-strand breaks is non-homologous end joining (NHEJ).

How NHEJ can repair DNA. DNA damage cuses either a single stranded or double stranded break. If it is a double stranded break, then NHEJ can "correct" the damage, but dome genetic information will be lost. — How NHEJ can repair DNA. Damage to DNA can cause Single Strand (SS) or Double Strand (DS) breaks. Non-Homologous End Joining can repair double stranded break, but also causes small deletions of DNA. Image by Eder Xhako, Created with BioRender

NHEJ occurs mainly when the cell is actively growing. Double-stranded breaks are very harmful to the cell. If left unrepaired, the break can make the whole DNA chromosome unstable, and result in death of the cell. In order to minimize the damage caused by the breaks, NHEJ is a very fast, although often imprecise, method of DNA repair. When DNA undergoes a double-stranded break, NHEJ will act like glue and stick the two broken DNA ends together. Depending on where the break occurred and how much damage happened, the repair can then either lead to a complete repair or the loss of some DNA base pairs at the junctions resulting in permanent deletions. It is more common for NHEJ to lead to small deletions rather than a precise repair. Depending on the location of the deletion, it can have either no consequence or be potentially damaging to a gene

How do scientists use NHEJ to their advantage?

Outside of the context of natural DNA damage, scientists have learned how to utilize the naturally occurring NHEJ repair pathway to inactivate genes of interest. As such, scientists have developed methods, such as the CRISPR-Cas9 system, to artificially introduce double-stranded breaks in essential and functional parts of the gene. The double-strand break then causes the cell to repair the double-stranded break using NHEJ. As NHEJ often leads to small deletions, which will damage the essential part of the gene, the gene will often be rendered non-functional. In this way, scientists can study what happens in the absence of the gene.

If you would like to learn more about Non-Homologous End Joining, take a look at this video by Oxford University Press.

Snapshot written by Eder Xhako and edited by Larissa Nitschke