DNA Damage and Repair:

 

Introduction:

 

The genomic DNA, in the cells, depending upon its location and function, is subjected to different hostile conditions, both within and from outside the cell. Changes in pH, and exposure to heat, toxic chemicals, irradiations, oxygen radicals and others, where each of them have severe effects on DNA and can cause considerable damage to DNA.  The DNA, such long molecules are really protected in chromosomes or chromatin for they are bound by histones and nonhistones most of the time except during replication; even bacterial DNA is bound by histone like proteins.

 

 

The damage to DNA can be in the form of modification of bases, addition of bulky adducts, change in the sequence of bases, loss of base, loss or addition of nucleotides, base dimrization, cross linking of bases, cross linking of complementary strands, break in one strand or in both strands, deletions, or any structural deformations are   bound to damage the encoded information, which in turn will have profound effect on the character of cell(s), tissues and ultimately affect an organism   as a whole.  Such changes may result in heritable genetic disorders.  Most of such damages are found localized in tissues, but such damages in gametic cell is most damaging and heritable.

 

 

Damages can be due to many mechanistic malfunctions during DNA synthesis; and DNA, which are like mismatch of base pairing, slippage type duplications, deletions, additions, duplications, translocations and inversions of different segments; all such changes can lead to irreversible damage and death of an organism or an organism can survive but with defects.  The long term changes, for many generations, in the genetic information can lead to elimination of the species or generation of new characters and a new variant, but left to natural selection; often the organism can select itself to the environment lead to speciation, which may have beneficial effects or deleterious effects.

 

Any change that is heritable is called mutation, which can be of multiple dimensions; it can affect single character, both physical and chemical, or it can affect the whole tissue or organ or disablement of an organ or body where the organism as whole suffers.  In the following discussions we will consider the causes and effects that cause genetic disorders and how organisms have inbuilt mechanisms to repair the damage instaneously.

 

Organisms, small or big, prokaryote or eukaryotes, have genetic information ingrained, say imprinted in the form of nucleotide sequence in DNA.   Any change in the information, whatever may be the type of change, is not desirable and it may affect the character of the gene product, which in turn may affect either the biochemical or physical character of the cell or tissue and the organism as whole.  Many of the heritable changes are called Mutations.  The meaning and the definition of terms like mutation and DNA damage are really indistinguishable and often blurred.   Any changes in the DNA, whatever may be the form of damage, if inherited, may result in defective function or no affect; detectable or undetectable are called mutations.  Any physical change to the DNA is generally accepted as ‘Damage’.  Any change in DNA that is heritable without much damage can also be considered as Mutation. The damage may result in minor changes in the information or it may drastically affect the function and form of an organism.

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