How do we fix DNA breakage accurately?

Jasper Ng
4 min readJan 11, 2020
(Credit: Adult Swim)🧬

In one episode of Adult Swim’s Rick and Morty, Morty kills a platoon of infantry by using a device to break their DNA. The soldiers either melted into slime or mutated into monsters.

Though this is obviously science fiction, DNA breakage can cause serious health problems in real life.

Some of the problems include cancer.

(Credit:National Cancer Institute)

9.56 million deaths world wide in 2017 are caused by cancer.

That is crazy. It means that basically out of every six people in the world that die, one died from cancer.

Cancer causing substances are called carcinogens. Carcinogens might damage the DNA directly or cause cells to divide rapidly which will make copying errors more likely to happen.

For example, smoking cigarettes have been shown to directly damage DNA. Chromium also allows harmful substances attach to DNA potentially damaging it. UV radiation is another carcinogen that is responsible for skin cancer.

External DNA damage and copying error are both part of DNA repair pathways.

Knowing this, our solution should be focused on improving the accuracy of our DNA repair.

Looking for solutions in nature…

A Tardigrade!

These little critters became very interesting to scientists due to their unusual hardiness. Certain species of Tardigrades such as R. varieornatus shows incredible tolerance to radiation without a high risk of developing cancer.

In an October 2019 study published in Nature, two tardigrades, r. varieornatus and h. dujardini, had their genome compared.

There are many interesting aspects in this paper but the focus will be on the following proteins.

  • Dsup (Damage Suppressor)
  • CHK1 variant p.F93Y
  • POLK variant p. S132G
  • RAD51

When comparing the two tardigrades, there were only copy number changes of DNA repair genes. This means that r. varieornatus only has more copies of DNA repair genes.

This tardigrade also have residue changes to certain genes. This means the an amino acid in a protein might be changed to another acid.

Damage Suppressor (Dsup)

This protein is present in both tardigrades at the same amount. It suppresses DNA damage from radiation up to about 40%. The difference in radiotolerance between the tardigrades was what suggested that the r. varieornatus has some other genes that improved radiotolerance.

CHK1

This is a protein coded from gene CHECK1. CHK1 is used for DNA damage response and homologous recombination. Homologous recombination is when cells share DNA sequences to repair broken parts. This protein has residue changes only in the r. varieornatus.

POLK

This is a polymerase protein that is found in humans. It makes errors frequently and especially when exposed to radiation. The r. varieornatus has the variant that may have improved the accuracy of this protein.

RAD51

This is a protein family that is responsible for repairing double strand breakage. The genes were expanded in the r. varieornatus.

What does CRISPR-Cas9 have to do with this?

Originally a bacteria immune system, viral DNA is cut and inserted into CRISPRs, which are a chain of DNA sequences. Cas9 is a protein cuts DNA. It is guided by a piece of RNA copied from a DNA sequence in the CRISPRs.

The CRISPR-Cas system allows scientists to edit DNA. Scientists use this by inserting the desired RNA sequence to Cas9 to guide it to cut a specific section DNA.✂️

The DNA can be repaired by using homology directed repair. This method uses a template DNA strand to guide the repairs.

What does this all mean?

This is the key part in making humans less prone to cancer. As we have identified important genes in tardigrades and we have the tools in order to edit our DNA, we can correct and add new genes that will significantly increase our accuracy of our DNA repair!🧬

I see this as an essential stepping stone for space exploration. Space exploration exposes astronauts to radiation which elevates the risk of cancer. Having higher radiotolerance would keep the astronauts healthier.

With humans being healthier and more hardy, we will be one step closer to a spacefaring sci-fi civilization.🚀

Takeaways

  1. Cancer is one of the world’s biggest problems.
  2. DNA breakage causes cancer
  3. Tardigrades have genes that enhance their DNA repair pathways
  4. Humans would be extremely resistant to cancer if these genes were introduced.

Gene editing has opened up so many doors and I really can’t wait to learn more about the field.

Join me on my journey by subscribing to my newsletter!

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