Distorted DNA
Our nuclear DNA genome is under constant attack from reactive chemicals that the cell generates as by-products of metabolism, as well as environmental threats as X rays, UV radiation from the sun, and immense chemical pollution, etc.
Missing few ‘letters’ can stop brain growth before age 30
Among the 100,000’s of mutations within the human genome, over 4,000 are known to be associated with genetic diseases or disorders, as well as aging. Cystic fibrosis and sickle cell disease can be caused by a single gene mutation.
Types of DNA Distortion
Different processes like hydrolysis, alkylation, de-amination, oxidation, and transcription are capable of causing changes among the ≈3.5 billion base-twins in the DNA molecule.
Hydrolysis
The chemical bond between a DNA base and its respective de-oxy-ribose, is subject to chance cleavage by a water molecule in a process known as spontaneous hydrolysis.
Loss of the purine base is referred to as de-purination. The loss of the pyrimidine base is called de-pyrimidination.
The now base-less sugars become AP-sites, A-Purinic or A-Pyrimidinic. They are potentially lethal to the cell, as they act to block the progress of DNA replication.
However, they are efficiently repaired in a series of enzyme-catalyzed reactions collectively referred to as the Base Excision Repair (BER) pathway. In fact, AP-sites are intentionally created during the course of BER:
De-amination
One form of modification of a base-pair’s chemical structure is ‘spontaneous de-amination’, the loss of an amino group (-NH2). Cytosine (C), paired with guanine (G) in normal DNA, has an amino group attached to its 4th carbon (C4).
When that amino group is lost, an uracil (U) base is formed, and a normal C-G DNA base pair is changed to a U-G base pair. Uracil is normally not a part of DNA.
During DNA replication, this uracil (U) will pair with a new adenine (A), while on the other strand the guanine (G) will pair with a new cytosine (C). Thus, one DNA double-strand contains a normal C-G base pair, but the other double-strand has a mutant U-A base pair instead of a G-C pair.
This process is called ‘mutation fixation’. The cell accepts now the new mutant U-A base pair as normal. About 400 cytosine de-amination events occur daily in our genome.
Repair before DNA replication commences, is vital. One cause of normal human aging is the gradual accumulation of mutations in our cellular DNA.
Alkylation
Another type of base modification is alkylation. This occurs when an alkyl group (like methyl -CH3 or ethyl -C2H5) is transferred to a DNA base. The nitrogen atoms of the purine bases (N3 of adenine and N7 of guanine) and the oxygen atom of guanine (O6) are particularly susceptible to alkylation in the form of methylation.
Methylation of DNA bases can occur through the action of environmental and intracellular agents. Chemicals such as di-methylsulfate, formed during the combustion of sulfur-containing fossil and N-methyl-N-nitrosoamine, a component of tobacco smoke, are powerful alkylating agents. These chemicals create mutations and cancer cells.
Inside every cell is a small molecule known as S-adenosyl-methionine or ‘SAM’. The function of SAM is to provide an activated methyl group for virtually every normal biological methylation reaction.
SAM helps to make important molecules such as adrenaline, a hormone secreted in times of stress; creatine, which provides energy for muscle contraction; and phosphate-idyl-choline, an important component of cell membranes.
However, SAM can also methylate the wrong targets, such as adenine and guanine. Such damage must be continually repaired to prevent mutation fixation.
Oxidation
High-energy radiation, like X rays and gamma radiation, causes oxidative DNA base damage by interacting with water molecules to create highly reactive oxygen species, which then attack DNA bases at susceptible carbon atoms.
Oxidative base damage is also produced by reactive oxygen species released during normal ‘respiration’ in mitochondria, the cell’s “energy factories.”
When levels of endogenous DNA damage, or exposure to harmful exogenous agents like radiation or toxic chemicals is high, the cell’s DNA repair systems become overwhelmed.
The result is a high mutation rate, which in turn may lead to cell death, cancer, and other diseases. The level of DNA repair activity declines with age, thus increasing the mutational burden of each cell.
Proton mutation
In rare cases, if the free proton of a Cytosine acid starts tunneling from its nitrogen atom in stead of its oxygen atom, then -from a quantum-information-perspective- its acts like a Thymine acid. Thus, an Adenine acid ‘sees’ it as a Thymine acid and will bond with it, causing a mutation.
EW Magnetic Fields
Extremely Weak Magnetic Fields can cause major changes in DNA. Those changes can be observed with a standard microscope, by very carefully counting the chromosomes.
The magnetic fields can change the speed of the protons through the ATPS water channels, and thus effect the chromosome count.
Promising Repair Solution
The current state-of-the-art gene-editing tool, known as CRISPR-Cas9, is extremely powerful, but its lack of precision, high error rate and limited scope hamper its ability to treat human genetic diseases.
Prime editing, is a versatile and precise genome editing method that directly writes new genetic info into a specified DNA site using a catalytically impaired Cas9 endo-nuclease fused to an engineered reverse transcriptase, programmed with a prime editing guide RNA (pegRNA) that specifies the target site + encodes the desired edit.
