Introduction:
Genetic variations are important for evolution but the survival of the individual demands genetic stability. Maintaining genetic stability requires an extremely accurate mechanism for replacing DNA and mechanism for repairing the many accidental lesions that occur continually in DNA.
Most such changes are temporary because they are immediately corrected by a set of processes that are collectively called as DNA repair.
DNA Damage
DNA damage is the alteration in the chemical structure of DNA, such as a break in a strand of DNA, a base missing from the backbone of DNA, a chemically changed base. Damage to DNA that occurs naturally can result from metabolic or hydrolytic processes.
Sources of DNA damage
Endogenous damage:
It includes damage from within the cell, it also includes replication errors
Example: Attack by reactive oxygen species produced from normal metabolic byproducts.
Exogenous damage:
It includes damage caused by external agents.
Examples:
- UV,X-rays and gamma rays.
- Plants of comfrey species.
- Viruses.
Causes of DNA damage
UV rays:
Random photons of ultraviolet light induce aberrant bonding between neighboring pyramidines( thymine and cytosine )bases on the same strand of DNA this will prevent the replication.
Methyl and ethyl group added to DNA bases alters the structure of DNA.
Deamination:
An amino group of cytosine is removed and the base become uracil.
An amino group of adenine or guanine is removed and the base becomes hyoxanthine.
The base is simply ripped out of the DNA molecule leaving a gap(like a missing tooth).
Consequences of DNA damage
- Leads to genome instability.
- Increased cancer risk.
- Accelerated ageing.
- Neurodegenerative diseases.
DNA Repair
DNA repair refers to the number of process by which a cell identifies and corrects damage to the DNA molecule that encode its genome.
Depending on the types of damage inflicted on DNA double helical structure, a variety of repair strategies have evolved to restore lost information.
Fallowing are the types of DNA repair mechanisms
1) Direct Repair:
This system act directly on damaged nucleotides and convert each one back to its original structure but only few damaged nucleotide can be repaired directly.
Pyramidine dimers are repaired by a light dependent direct system called photoreactivation.
It involves excision of a segment of the polynucleotide containing a damage site, followed by resynthesis of the correct nucleotide sequence by a DNA polymerase.
Excision-''Resynthesis-Ligation.
Excision repair is of two types:
a) Base excision repair
b) Nucleotide excision repair
a) Base excision repair:
BER repairs damage to a single base caused by oxydation, alkylation, hydrolysis, or deamination.
The damaged base is removed by a DNA glycosylase, resynthesized by a DNA polymerase, and a DNA ligase performs the final nick sealing step.
2) Nucleotide excision repair:
Nucleotide excision repair recognizes bulky helix distorting lesions such as pyrimidine dimers and 6, four photoproducts and treats them.
Mismatch repair corrects errors of DNA replication and recombination that results in mispaired but undamaged nucleotide.
4) Recombinational repair:
Recombinational repair requires the presence of an identical or nearly identical sequence to be used as a template for repair of the break in the DNA strand.
The enzymatic machinery responsible is nearly identical to the machinery responsible for chromosomal crossover during meiosis.
