DNArepair is a mechanism that a cell uses to amend damaged or mismatched segmentson its sequence. Our cells are constantly exposed to insults from endogenousand exogenous agents that can introduce damage into our DNA and generategenomic instability. Many of these lesions cause structural damage to DNA andcan alter or eliminate fundamental cellular processes, such as DNA replicationor transcription (Dexheimer, 2013).DNA,like any other molecule, is subject to chemical reactions. DNA damage may resultfrom either intrinsic or extrinsic agents.
In general, the vast majority of DNAmodifications are endogenous in origin. The simplest form of endogenous DNAdamage is spontaneous hydrolysis. DNA is also susceptible to chemicalmodification by reactive molecules that are created during normal cellularmetabolism. An additional type of DNA damage related to endogenous reactivemolecules is alkylation. The putative candidates of such agents include theendogenous methyl donor, S-adenosylmethionine, nitrosated amines, and methylradicals generated by lipid eroxidation. The primary sites of alkylation arethe O? and N-atoms of nucleobases (Dexheimer,2013).DNA REPAIR MECHANISMSAcase study of Deinococcus radiodurans;this microorganism has the ability to repair its genome after it has beenblasted apart by a high dose of radiation might be a contender.
Surprisingly,this ability is primarily related to the resistance of D. radiodurans proteins and the structure of its genome, ratherthan to its DNA repair mechanisms. Its radiation-resistant proteins are able tobegin repairing the genome quickly.
Repair is aided by the genome consisting oftwo chromosomes, each having numerous areas of homology. This allows the DNAfragments to anneal to each other, facilitating the piecing together of theshattered genome. Other than this, D.
radiodurans uses almost the same DNA repair mechanisms as other microorganisms.Clearly, mutations can have disastrous effects. Therefore it is imperative thata microorganism be able to repair changes. E.coli is another example of microorganism that carryout DNA repairs (Willey, et al,2014).
Generally,to properly manage deleterious consequences of DNA damage, the cells developedseveral repair mechanisms which eliminates genomes mis-instructive ornon-instructive elements, as well as seal DNA breaks (Dexheimer, 2013). The cells initiate processes such as Proofreading, Mismatch repair, Excisionrepair, Direct repair and Recombinant repair.Proofreadingwhich is a function of DNA polymerase III checks for errors such as mismatchesof nucleotide bases and corrects them (Kornberg and Maki, 1987).
This mechanism also acts as the first line ofdefense. DNA polymerases have the ability to evaluate the hydrogen bonds formedbetween the newly added nucleotide and the template nucleotide, and correct anyerrors immediately. When a DNA polymerase detects that a mistake has been made,it backs up, removing the incorrect nucleotide with its 3′ to 5′ exonucleaseactivity. It then restarts DNA replication, this time inserting the correctnucleotide.
Proofreading is very efficient, but it does not always correcterrors in replication. Furthermore, it is not useful for correcting inducedmutations (Willey, et al, 2014).Mismatchrepair is essential to all organisms because itmaintains the stability of the genome during repeated duplication (Jun, et al, 2006). When proofreading byreplicative DNA polymerases fails, mismatched bases are usually detected andrepaired by the mismatch repair system. In E.
coli the enzyme MutS scans thenewly replicated DNA for mismatched pairs. Another enzyme, MutH, removes astretch of newly synthesized DNA around the mismatch. A DNA polymerase then replacesthe excised nucleotides, and the resulting nick is sealed by DNA ligase (Willey, et al,2014). Excision repair correctsdamage that causes distortions in the double helix. Two types of excisionrepair systems have been described: nucleotide excision repair and baseexcision repair.
They both use the same approach to repair: Remove the damaged portionof a DNA strand and use the intact complementary strand as the template forsynthesis of new DNA. They are distinguished by the enzymes used to correct DNAdamage. Nucleotide excision repair uses UvrABC endonuclease, which baseexcision repair uses DNA glycosylase.
Both enzymes and repairs are applicableto E.coli repair mechanism (Willey, et al,2014).Directrepair corrects Thymine dimers and alkylatedbases.
Thus, damage to guanine from mutagens such as methyl-nitrosoguanidine canbe repaired directly. For instance, photoreactivation repairs thymine dimers(figure 16.5) by splitting them apart with the help of visible light. Thisphotochemical reaction is catalyzed by the enzyme photolyase (Willey, et al,2014).
Recombinant repaircorrects damaged DNA in which both bases of a pair are missing or damaged, orwhere there is a gap opposite a lesion. In this type of repair, a proteincalled RecA cuts a piece of template DNA from a sister molecule and puts itinto the gap or uses it to replace a damaged strand (Willey, et al, 2014). CONCLUSIONThegenetic and biological significance of DNA repair mechanisms is underscored bythe fact that their deregulation of DNA repairs can lead to the initiation andprogression of genetic disorders. On the other hand, DNA repair can conferresistance to front line antibiotics, cancer treatments (i.
e. chemotherapy andradiation), which rely on the generation of DNA damage to kill pathogenic liveforms or cancerous cells. The repair mechanisms serve as a method of survivalto the cell and also a way of retaining or attaining the normal state ofcellular stability. However, DNA repair mechanisms sometimes are not be able tocorrect errors and breaks especially when these errors and breaks are induced.