DNA Repair Enzymes – Part I: The basics. | BareFacedTruth.com

DNA Repair Enzymes – Part I: The basics.

Recently, several BFT readers asked that we write about DNA repair enzymes, and their benefits when applied to the skin. To do that, we must first take a little trip.

So tighten your seat belt. In order to dive into the science of DNA, we must first dive deep into the interior of nucleated cells – your body has trillions of them.

So, what are DNA repair enzymes, what do they do and what can they do for the skin? Let’s start with the basics and then move onto some more detailed information, some of it very detailed.

(We apologize in advance: this is complex science and the details are important.)

Not exactly the happiest thought, but one that is 100% true. Our extrauterine life is a continuum that starts with our first breath and ends with our last. Throughout our numbered days, our bodies are under constant assault, with some of the most potentially lethal assaults invisible ones that take place at a level so infinitesimally small, it boggles the mind.

It takes a hugely powerful electron microscope to plumb this world. It is the realm of atoms and molecules. Specifically, the molecular structures that give us life and make us unique among all the world’s creatures – our own and very personal DNA.

WHAT IS DNA?

DNA, or deoxyribonucleic acid, is the hereditary material in humans and almost every other organism on the planet. Nearly every cell in an individual person’s body has the same DNA, and it’s different from the DNA of every other human being. We are each unique. The great majority of DNA is located in the cell nucleus (where it is called nuclear DNA), although a small amount of DNA is also found in mitochondria (where it is called mitochondrial DNA or mtDNA).

The information in DNA is stored as a code made up of four chemical bases: adenine (A), guanine (G), cytosine (C), and thymine (T). Human DNA consists of about 3 billion bases, and more than 99 percent of those bases are the same in all people. The order, or sequence, of these bases determines the information available for building and maintaining an organism, similar to the way in which letters of the alphabet appear in a certain order to form words and sentences.

DNA bases pair up with each other, always A with T and always C with G, to form units called base pairs. Each base is also attached to a sugar molecule and a phosphate molecule. Together, a base, sugar, and phosphate are called a nucleotide. Nucleotides are arranged in two long strands that form a spiral called a double helix. The structure of the double helix is somewhat like a ladder, with the base pairs forming the ladder’s rungs and the sugar and phosphate molecules forming the vertical sidepieces of the ladder.

DNA MAKES IDENTICAL COPIES OF ITSELF – OVER AND OVER AGAIN

An extremely important property of DNA is that it can replicate or make copies of itself. Each strand of DNA in the double helix can serve as a pattern for duplicating the sequence of bases. This is critical when cells divide because each new cell needs to have an exact copy of the DNA present in the old cell.

As adults, we have many times more cells than we do at birth. Yet, the DNA in all our adult cells is identical to that of our very own first cell, the fertilized egg from which we evolve, that single specific egg and specific sperm that united to give us life and make each of us unique.

WHAT IS A GENE?

A gene is the basic physical and functional unit of heredity. Genes, which are made up of DNA, act as instructions to make specific protein molecules. In humans, genes vary in size from a few hundred DNA bases to more than 2 million bases. The Human Genome Project has estimated that humans have between 20,000 and 25,000 genes.

Every person has two copies of each gene, one inherited from each parent. Most genes are the same in all people, but a small number of genes (less than 1 percent of the total) are slightly different from the genes found in every other individual person.  Alleles are forms of the same gene with small differences in their sequence of DNA bases. These small differences contribute to each person’s unique physical features. Chromosomes are the structures within the nucleus of our cells that carry our genetic information. At fertilization, one sperm combines with one egg, so that one chromosome of each pair is donated by the egg and the other by the sperm.

 

In humans, each cell contains 23 pairs of chromosomes, for a total of 46. Twenty-two of these pairs, called autosomes, look the same in both males and females. The 23rd pair, the sex chromosomes, differ between males and females. Females have two copies of the X chromosome, while males have one X and one Y chromosome. The DNA material in a chromosome is coiled and folded very compactly around special proteins called histones.

PACKED LIKE SARDINES

The double helix of DNA is highly negatively charged due to all the negatively charged phosphates in the backbone. All that negative charge must be counterbalanced by a positive charge, and the cell makes proteins called histones that bind DNA and aid in DNA’s packaging. Histones are positively charged proteins that wrap up DNA through interactions between their positive charges and the negative charges of DNA. Double-stranded DNA loops around 8 histones twice, forming the nucleosome, which is the building block of chromatin packaging.

DNA can be further packaged by forming coils of nucleosomes, called chromatin fibers. These fibers are condensed into chromosomes during mitosis, the name for the process of cell division. However, packaging of chromatin into chromosomes that we are most familiar with occurs only during a few stages of mitosis. Most of the time, DNA is very loosely packaged.

Astonishingly, if unwound and stretched into a single strand, all the DNA in the body would reach back and forth from the Earth to the Sun – 70 times! It is thin but very, very, very, very long!

 

Sorry, dear, your ten minutes is up…it’s time to divide.

 

HOW IS DNA DAMAGED? WHAT HAPPENS IF IT IS?

 DNA damage, is due to environmental factors and the normal metabolic processes that occur inside the cell. Damage occurs at a rate of 10,000 to 1,000,000 molecular lesions per cell per day! While this constitutes only 0.000165% of the human genome’s approximately 6 billion bases (3 billion base pairs), unrepaired lesions in critical genes (such as tumor suppressor genes) can impede a cell’s ability to carry out its function and appreciably increase the likelihood of tumor formation.

The rate of DNA damage and repair is dependent on many factors, including the cell type, the age of the cell, and the extracellular environment. A cell that has accumulated a large amount of DNA damage, or one that no longer effectively repairs damage incurred to its DNA, can enter one of three possible states:

  1. an irreversible state of dormancy, known as senescence.
  2. cell suicide, also known as apoptosis or programmed cell death.
  3. unregulated cell division, which can lead to the formation of a tumor that is cancerous.

The DNA repair ability of a cell is vital to the integrity of its genome and thus to the normal function of that organism. Many genes that were initially shown to influence life span have turned out to be involved in DNA damage repair and protection.

 

More about that in Part Two.

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