DNA Damage Repair Mechanisms

Damaged DNA often needs to be repaired for the organism to survive. These are three common DNA repair mechanisms.

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Deoxyribonucleic acid(DNA) is often damaged by outside mutagens resulting in damages within the DNA segment.  Though some damages are not caught by the cell, most are corrected as easily as possible.  Three main ways cells repair these damages/mutations are by mechanisms called direct reversal, base-excision repair, and nucleotide-excision repair. These three mechanisms repair damaged DNA in various ways.

Direct reversal of mutated DNA-

            Direct reversal is the most direct and easiest way to repair simple DNA damage, such as DNA that has been damaged by UV light. When UV light comes into contact with the DNA it can cause a photodimer.  Photodimers result from pyrimidines on one strand of DNA binding with an adjacent pyrimidine.  The cell recognizes photodimers using specific enzymes, and those enzymes bind to the site of mutation.   The enzyme then uses energy obtained from light, and separates the photodimers, giving the bases back their original conformation.

Figure 1: Formation of photodimer

Base-excision repair-

            Base-excision repair is a mechanism that is used to remove nonbulky damage to bases, such as methylation or deamination. The first step in base-excision repair is the binding of DNA glycosylases to the damaged DNA site. These enzymes cleave the bond between the base and the backbone, leaving a vacancy in the DNA sequence.  AP endonuclease then nicks the backbone structure at this vacancy, allowing for deoyribophosphodiesterase to attach to the damaged DNA and add the complementary base to the cut backbone.   This enzyme uses antiparallel complementarity to add the correct base to the site that previously had the mutation.  As it adds bases, old bases are removed in a long segment.  After the enzyme is done adding bases, DNA ligase comes in to seal the remaining nick in the DNA backbone, thus completing base-excision repair.

Figure 2: Base-excision repair

Nucleotide-excision repair-

            Nucleotide-excision repair is used much like base-excision repair, except on a larger scale. Nucleotide-excision repair is a mechanism the cell uses in order to repair bulky (longer) segments of damaged DNA. The cell first recognized damaged DNA either during transcription, or with the aid of certain enzymes. A multiprotein complex then binds at the damages section and cuts the backbone both upstream and downstream of the damaged DNA. The section of DNA that is damaged and was cut, is then removed from the DNA double helix so new bases can be added by polymerase. Ligase then seals the nick left at the end of the newly synthesized repair. The main difference between nucleotide-excision repair and base-excision repair is that base-excision repair cuts the bond between the base and the backbone so the base can be removed. The gap produced by the removal of the base is used for new strand synthesis. In nucleotide-excision repair however, the sugar phosphate DNA backbone is cut in two places and the damaged strand segment is completely removed before a new strand is synthesized.

Figure 3: Nucleotide-excision repair

 

These mechanisms are just three of many ways cells recognize and repair damaged DNA.  Many more have been discovered and deserve studying. 

Griffiths A, Wessler S, Carroll S, Doebley J. Introduction to Genetic Analysis tenth ed. W. H. New York:Freeman and Company.  2012.

Images from:

Wikipedia.com

http://bio3400.nicerweb.com/Locked/media/ch15/nucleotide_excision_repair.html

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