Improving human DNA repair using a tiny tardigrade

The tardigrade is a microscopic animal that can withstand several extreme environmental conditions, including high-intensity ionizing radiation. The study shows that this resistance is made possible by an extremely efficient enzymatic DNA repair system, which could be used as inspiration for treating human diseases.

During the evolution of life on Earth, all species must have acquired characteristics that maximize their likelihood of surviving and passing on their genes to their offspring.

From a scientific perspective, there is enormous interest in studying these adaptation mechanisms, not only to improve our knowledge of the world around us, but also to identify specific molecular processes that could be applied to treat diseases afflicting humanity.

Invincible bear cubs!

Tardigrade is a good example of an animal that, although evolutionarily very distant from humans, has several intriguing characteristics that have therapeutic potential.

The tardigrade, nicknamed the “water bear”, is a tiny animal (0.1 to 1.5 mm long) that has incredible resistance to several extreme environmental conditions that are detrimental to all living organisms, be it extreme temperatures (from – 270°C to +150°C). , lack of atmospheric pressure or, conversely, overwhelming pressure, lack of water and food, or even high-intensity ionizing radiation (X-rays or ultraviolet rays).

The last case is especially interesting: tardigrades have been shown to be able to survive radiation of 5000-6000 Gray (Gy), i.e. 1000 times the lethal dose for humans.

Large-scale renovation

Recent research provides insight into the biochemical mechanisms responsible for adaptation to radiation. ⁽¹⁾ In this study, researchers observed for the first time that the impact of a tardigrade species (Hypsibius exemplary) at high doses of gamma radiation (4360 Gy) caused significant damage to their DNA in the short term, but the animal recovered quickly with complete repair of these molecular breaks over the next 24 hours.

Further analysis showed that this recovery correlated with an increase in the expression of several genes, in particular enzymes involved in DNA repair.

In some cases, the increase in expression of these genes is of extraordinary magnitude, never seen in studies of this type. The levels of some genes increased more than 300-fold after irradiation, reaching levels of those involved in maintaining the animal’s basic biological functions, an exceptional phenomenon.

Highly qualified repairmen

An important question is whether these genes, which are involved in tardigrade DNA repair and radiation resistance, could perform a similar protective function if introduced into the cells of another organism.

Initial results obtained by researchers suggest that yes: the use of bacteria coli As a model, they observed that introducing these genes significantly increased the survival of bacteria when exposed to a huge dose of gamma rays, suggesting that they were sufficient to confer radiation resistance, regardless of the origin of the DNA.

These ultra-efficient DNA repair enzymes could be used to treat certain human pathologies associated with irreversible DNA damage, such as some rare genetic diseases that cause premature aging, or to repair mutated DNA after excessive exposure to sunlight.

These repair enzymes can also be used to minimize the side effects of radiation therapy on healthy tissue surrounding tumors during cancer treatment.

Another example demonstrating that the simplest forms of life are necessary for the survival of the most complex ones.

♦ (1) Clark-Hachtel CM et al. “The tardigrade Hypsibius exemplaris dramatically activates DNA repair pathway genes in response to ionizing radiation.” Well. Biol.published April 24, 2024