Gigi Minsky and Dr. Peter Sykora

 

 

Within the cells of all living organisms, from the brain and skin cells of animals, to plant and fungal cells, resides a genetic “blueprint” in the form of chromosomes, made up of DNA. DNA damage is an unavoidable aspect of life that plagues all oxygen utilizing organisms, that accumulates over time as we age.

 

 

 

 

 

DNA is constantly accumulating DNA damage from various sources. There are endogenous and exogenous DNA damage sources. Exogenous sources, such as solar radiation, alcohol and exposure to industrial pollution can be somewhat avoided. Endogenous sources, such as accumulation of ROS (reactive oxidation species) or mismatches of DNA base pairs occur naturally as a byproduct of respiration and replication.

 

 

DNA is the only biological macromolecule that is repaired. Common functions of DNA repair pathways include:

 

Recognition

Reinforcement/Recruitment

Removal

Reconstruction

Reinstatement

 

 

 

There are hundreds of different forms of DNA damage. A single cell may repair 50,000 errors from oxidative DNA damage, such as single stranded breaks or small nucleotide modifications. However, if it suffers more than a few double stranded breaks (DSB) the cell will die. Hence not all DNA damage is the same. There are many forms of DNA repair to be able to compensate for all the forms of DNA damage.

 

 

 

 

 

Not all cells repair DNA damage in the same way. The more differentiated a cell becomes, the less repair pathways it has available. Stem cells use largely “error free” repair pathways- if they accumulate mutations, they can quickly become cancerous. However, a terminally differentiated neuron is unlikely to enter back into cell-cycle and become cancerous, thus the repair pathways it uses are more limited and more error-prone. Mutation is what happens when repair is ineffective.

Once a mutation is replicated, it becomes integrated into the stable genome and can no longer be identified or repaired.

 

 

 

 

Naturally occurring DNA modification mechanisms such as CRISPR/Cas9, TALEN or ZFN. are harnessed in biotechnology/bioengineering to create genome edits.

At Amelia Technologies we harness the mechanisms of DNA repair to create tools and solutions for the rapidly expanding aging research community.

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