DNA Damage and Repair

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DNA is the mechanism by which all of our physical characteristics and an increasingly large number of proven mental and social characteristics are passed on from one generation to the next.  This applies to all living organisms, with the exception of a few basic forms, which use RNA to pass on their genetic information and thus characteristics, from one generation to the next.

As the genetic information is passed on between parent and offspring and during the course of an individual organisms lifetime, damage can and does occur to the DNA and thus to the genes.  This damage as it occurs can result (depending also on a number of prevailing environmental factors) in the evolution of a species.  This is broadly done in general accordance with the principles of Charles Darwin’s Natural Selection.  When this damage occurs in a cumulative way through the course of an individual organisms lifetime however, the process eventually results in aging of the cells, tissues and organs, resulting eventually in cellular senescence and death.

A number of mechanisms have evolved in order to repair the damage to an organisms DNA.  The purpose of this section of the site is to outline the different types of damage that can occur to DNA and what mechanisms are in place to limit the affects of this damage and to repair damage once it inevitably does occur.

So before outlining the state of the art knowledge on this very broad subject, here first are a few definitions.

Definition of DNA

Deoxyribonucleic acid; a nucleic acid that consists of two long chains of nucleotides twisted together into a double helix and joined by hydrogen bonds between complementary bases adenine and thymine or cytosine and guanine; it carries the cell's genetic information and hereditary characteristics via its nucleotides and their sequence and is capable of self-replication and RNA synthesis.  http://www.answers.com/topic/dna

Note that where animal research is concerned, a distinction needs to be made between the DNA contained in the Nucleus of the cell, coiled up around beadlike histone proteins and coiled further into chromosomes and the DNA of the Mitochondria.  To aid in this distinction, please find below a definition of Mitochondrial DNA (mtDNA).

Definition of Mitochondrial DNA

Mitochondrial DNA (mtDNA) is DNA that is located in mitochondria. This is in contrast to most DNA of eukaryotic organisms, which is found in the nucleus. It is often stated that 100% of the mtDNA contribution to a zygote is inherited from the mother, although this is controversial and may not be true for all organisms.

Unlike most of the cell, the function of which is defined by nuclear DNA, mitochondria have their own DNA and are assumed to have evolved separately. Human mitochondrial DNA consists of 5-10 rings of DNA and appears to carry 16,568 base pairs with 37 genes (13 proteins, 22 tRNAs and two rRNAs) which are concerned with the production of proteins involved in cellular respiration. However many proteins found in the mitochondria are encoded by nuclear DNA: some, if not most, are thought to have been originally part of the mitochondrial DNA but have since been transferred to the nucleus during evolution.

There is little change in the mtDNA from parent to offspring, unlike nuclear DNA which changes by 50% each generation. Since the mutation rate is easily measured, mtDNA is a powerful tool for tracking matrilineage, and has been used in this role for tracking many species back hundreds of generations.  http://en.wikipedia.org/wiki/Mitochondrial_DNA

A Summary of DNA Damage and Repair

DNA repair is an integrated process whereby damage to the DNA of the cells genome is identified and then corrected.  This DNA damage can occur as a result of a large number of normal metabolic activities.  For example free radicals such as Hydrogen Peroxide H2O2 produced during cellular respiration can damage DNA quite severely.  Also a variety of environmental factors, such as UV radiation and carcinogenic chemicals can and do result in damage to DNA.

This damage can result in lesions that may prevent the cell from being able to transcribe its genes, resulting in a loss of functionality of the cell.  Other lesions can cause damage which does not affect the functionality of the cell itself, but does have an affect on any daughter cells that are produced following Mitosis.  Perhaps resulting in the daughter cells functioning abnormally or being unable to survive.

Fortunately there are a number of DNA repair processes which strive to limit the affects of this damage.  DNA repair is not perfect however.  This means that over time the repair process will fail and a cell will enter one of the following states.

1.  Apoptosis or cellular suicide.  This is a process by which the cell destroys itself
2.  Senescence.  A process whereby the cell becomes irreversibly dormant
3.  Uncontrolled cellular division.  This can result in tumor formation and cancer

The effectiveness of the DNA repair mechanisms in a species have a direct relation to the average and maximum life expectancy of that species.

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    The subject known as Gerontology is the study of the process of aging throughout the lifespan of an individual. This multi-disciplinary subject analyses a variety of aspects of aging, including the physical, mental and social changes in individuals as they grow older. Professionals from a variety of diverse, but interconnected fields are known collectively as gerontologists.

    Gerontology covers such varied subjects as the effects of our aging population on society, including the financial effects of pensions, health insurance and retirement planning. How society itself views the elderly is also encompassed in this field.

    Gerontology distinguishes itself from geriatrics, the branch of medicine that studies the diseases of the old.

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    Rhonda Watson

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