Understanding The Basics Of DNA Repair
All living organisms must have the ability to repair changes that occur in the structure of DNA in order to minimize mutation.
Living cells contain several DNA repair systems that can fix different types of DNA alterations.
DNA repair requires two coordinated events.
- In the first step, one or more proteins in the repair system detect an irregularity in DNA structure.
- In the second step, the abnormality(mutation) is repaired.
Rate of Repair
The rate of DNA repair is dependent on many factors, including the cell type, the age of the cell, and the extracellular environment. A cell that has accumulated a large amount of DNA damage, or one that no longer effectively repairs damage incurred to its DNA, can enter one of three possible states:
- An irreversible state of dormancy, known as senescence.
- Cell suicide, also known as apoptosis or programmed cell death.
- Unregulated cell division, which can lead to the formation of a tumor that is cancerous.
Sometimes DNA is modified by the attachment of an alkyl group, such as –CH2CH3, to a base. In direct repair, an enzyme removes this alkyl group, thereby restoring the structure of the original base.
The altered DNA is removed and a new segment of DNA is synthesized.
|A repair enzyme recognizes an incorrect structure in the DNA and directly converts it back to a correct structure.|
Base Excision & Nucleotide Excision Repair
|An abnormal base or nucleotide is recognized and a portion of the stand containing the abnormality is removed. The complementary DNA strand is then used as a template to synthesize a normal DNA strand.|
Methyl-Directed Mismatch Repair
|Similar to excision repair except that the DNA defect is a base pair mismatch in the DNA, not an abnormal nucleotide. The mismatch is recognized, and a strand of DNA in this region is removed. The complementary strand is used to synthesize a normal strand of DNA.|
Nucleotide Excision Repair Systems Remove Segments of Damaged DNA
One of the most common types of DNA repair systems is nucleotide excision repair (NER), which can fix many different types of DNA damage, including UV-induced damage, chemically modified bases, missing bases, and various types of cross-links.
In NER, a region surrounds several nucleotides in the damaged strand, is removed from the DNA, and the intact undamaged strand is used as a template for re-synthesis of a normal complementary strand.
NER is found in all eukaryotes and prokaryotes.
Mismatch Repair Systems Recognize & Correct a Base Pair Mismatch
Another types of abnormality(mutation) that should not occur in DNA is a base mismatch, in which the structure of the DNA double helix does not obey the AT/GC rule of base pairing.
During the normal course of DNA replication, DNA polymerase may add an incorrect nucleotide to the growing strand by mistake.
This creates a mismatch between a nucleotide in the parental strand and one in the newly made strand. Various DNA repair mechanisms may recognize and remove this mismatch.
DNA polymerase has a proofreading ability that can detect mismatches and remove them. If this proofreading ability fails, cell contain additional DNA repair systems that can detect base mismatches and fix them.