It is a major understatement to say that cell replication is a complex activity. Generation of a new cell really is like “starting over,” but this beginning is a bootstrap operation. DNA Polymerase is key to getting from one cell to two replications based on that originating cell’s resources. Deoxyribonucleic acid (e.g., your DNA) is the key to building every living organism, but it originates in the previously existent cell, the “mother cell,” if you will. In some sense, the resulting reduplication produces new cells, the “daughters” of that previous autonomous cell. DNA Polymerase guides replication and insertion of cell chromosomes into the trait carrier code comprising genetic information in the daughter cells.

You know that none of us carries the only load in life. We often need help for the hard tasks. DNA is not a lone actor in the genetics of cell regeneration. It too needs help to accomplish the duplication of cells. It is a natural process that employs additional programming and materials (DNA Polymerase) to facilitate the process of generating DNA copies and inserting copied units in appropriate order into the new DNA strings destined to govern the functioning of new daughter cells’ operation in life.

Central Question.

So, let’s look at DNA Polymerase and its interface with a cell’s metabolism as new DNA is generated by creation of fresh copies of a mother cell’s genetic code. What is this DNA Polymerase? And, what does it do? Is there anything else?

DNA Building Components.

Legos are a very common successor to the old tinker toys that you no doubt were exposed to while growing up. Their concept was simple. You basically take a variety of basic units, connect them together, and develop a new construction comprised of multiple pieces. You can think of nucleotides as molecules generated by organisms. These nucleotide molecules are part of the DNA replication process. They function as units that are formed into nucleic acid polymers. These are your deoxyribonucleic and your ribonucleic acids. In your DNA these form sugar, phosphate, and nitrogenous molecules. The nitrogenous molecules link with Thymine, Cytosine, Adenine, or Guanine, to comprise the ultimate units of your nucleic acid in the genes of your DNA.

Putting Components Together.

The DNA Polymerase enzymes organize, group, and establish order for nucleotides, these building blocks of DNA and RNA. Helicase, another enzyme, untangles the DNA double strands and untangles the double helix. RNA and DNA bases comprise “primers” that initiate formation of new DNA strands by the DNA Polymerase. The DNA Polymerase enzymes add nucleotides to the initiated newly forming strands. They pair up with the mother cell’s original DNA strands where they copy the mother cell’s DNA. Where there was one strand before this process, there are now two. The DNA Polymerase verifies the accuracy of the copy that ultimately provides the DNA for daughter cells.

A Family of Enzymes.

The DNA Polymerase is not a single entity. There are “DNA Polymerases.” This family is divided according to function. Analysis of sequencing and internal structure define seven related Families, A, B, C, D, X, Y, and RT.

• Family A includes polymerases involved in DNA string copying or repair. They replicate by matching DNA components to the template being copied, always combining cytosine and adenine with guanine and thymine, respectively. This family has a “proofreading” capability to correct mismatches, assuring that mother and daughter DNA are accurate copies. This family is involved in reduplication of mitochondrial DNA in some single cell animals.
• Family B components process DNA replication during the actual cell division process, providing synthesis of DNA strands during the DNA copying activity. Family B also has copy-protection functions. These polymerases facilitate DNA duplication in some bacteriophages, plants, and fungi.
• Family C is the active replicative polymerases for bacteria. In duplication, this Family manages both leading and lagging strands of DNA.
• Family D is primarily replicative and appears active in life forms that are at the extremes of our biosphere, e.g., Euryarchaeota, hyperthermophiles, etc.
• Family X facilitates repair of damaged DNA. Like Family A, it patches eukaryotic cells. The Family reconstructs breaks related to chemical damage (e.g., hydrogen peroxide) and ionizing radiation. Its terminal deoxynucleotidyl transverse component is able to reconstruct lymphoid tissues.
• Family Y also has ability to repair DNA by reconstruction. It may repair DNA replication that has been halted by inappropriate generation of error DNA. It may allow repair of DNA even when errors are present in the string being copied.
• Family RT enable integration of DNA into a cell’s RNA, essentially using that RNA to create “synthetic” DNA. Cells taken over by virus activity, the so-called “retro-viruses” utilize Family RT.

“Synthetic” DNA Polymerase.

Altering DNA appears to be a way of reaching into “new creation.” The motivation or idea behind the study of genetics has been to discover “something better,” a new beer easier to brew, a new antibiotic, a new answer to cancer, and the like. The gene editor known as CRISPR has been employed to basically become a synthetic, controllable DNA Polymerase. In recent months, “EvolvR” (a gene editor allowing alterations in the form element gene code using CRISPR) has caught the interest of genome researchers.

“Natural selection” is the force lying behind the current thinking on evolution. Change in the form of evolution results when there is a form that survives and rivals competing members of an evolution group. Natural selection results in the “survival of the fittest,” but there may be many failures getting to the point of developing that “fittest member.” EvolvR speeds us the time line getting to that desirable endpoint.

Editing a whole DNA string is not particularly practical since it may result in mother and daughter cell destruction. EvolvR looks at editing just one gene at a time. Editing of a single gene has the potential to result in many variations. Developers suggest that evolution can be enhanced dramatically. EvolvR pairs Cas9 to that DNA Polymerase we’ve been discussing, allowing editing of just one of the two DNA strings in the double helix comprising a cell’s DNA. EvolvR “nicks” one strand, the DNA Polymerase replaces that DNA with a new piece via CRISPR, and the applied evolution is complete. Multiple experiments can be completed at a time and evaluated for utility within a day.

This methodology bypasses random DNA experiments and the problem of alteration of a double DNA intervention where many altered DNA organisms fail to thrive or even live. Developers of EvolvR suggest this CRISPR-related tool does not appear to have species limitations. In a sense, EvolvR has potential to be a successful synthetic DNA Polymerase with great potential for changing cellular dynamics.

Bioethics and DNA.

We have reached a point where we may be able to change what we thought was unchangeable. DNA Polymerase and synthetic versions of it may shortly change our scientific understanding of normal change and healing. We may be at the cusp of a new field within Bioethics and the use of the machinery of change in the biosciences.

Further Reading

• On Bioethics: https://practicalbioethics.org/what-is-bioethics  
• On CRISPR and EvolvR: https://phys.org/news/2018-08-crispr-diversifies-nowevolve.html   
• On DNA-Polymerase: https://www.news-medical.net/life-sciences/What-is-DNA-Polymerase.aspx  
• On DNA-Polymerase-Families: https://www.news-medical.net/life-sciences/DNA-Polymerase-Families.aspx

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