DNA repair refers to any of a number of biochemical processes in place for the purpose of repairing damage done to DNA sequence and structure in living organisms. Without DNA repair systems, living organisms would age extremely quickly, never being able to reach sexual maturity and propagate their species; thus, DNA repair is a vital element of any living organism.
Damage to DNA can occur in one of two general ways.
- Single base changes affect the sequence of base pairs in a piece of DNA, but doesn't affect the overall structure of DNA. As a result, virtually all normal operations on a piece of DNA (such as transcription or replication) go on as though nothing has happened. This usually happens when a chemical reaction changes the structure of one of the base pairs in the genetic sequence, or when an error occurs when the piece of DNA is being replicated and an extra or incorrect base pair is inserted into the sequence. This type of error usually results in the production of incorrectly formed proteins and enzymes from the incorrect recipe.
- Structural distortions provide a physical impediment to normal replication and transcription. Extra chemical bonds formed between atoms in a DNA sequence are the usual cause of this type of distortion. Essentially, this type of change causes replication and transcription to halt until they are fixed.
To fix these problems, eukaryotic systems have developed a number of methods for recognizing distortions in the DNA and fixing these distortions. Each cell usually has several different methods for dealing with these errors, to minimize the number of potential problems that might go unchecked.
The first type of repair system is direct repair, in which the damage is either directly removed or reversed. Errors are usually discovered in this method in a somewhat random fashion, usually during the earliest stages of transcription or replication. This method is actually rather rare, and usually involves an enzyme removing those bonds which shouldn't be there or adding ones that should be.
A more interesting method of repair is excision repair. Excision repair involves an enzyme that travels along a strand of DNA, looking for errors. When one is found, the enzyme sends chemical signals to other enzymes, which then help to excise the piece of DNA that is errant and synthesize a new, correct piece; this piece is then inserted. The enzymes are quite complex, and as a result this system is able to handle a wide variety of errors. Thus, this system usually appears in duplicate or triplicate in every cell and takes care of the vast majority of errors.
Mismatch repair usually occurs as transcription or replication is ending; the newly produced DNA and RNA is checked over for base pairs that do not have the right partner. When this occurs, an enzyme distinguishes between the older template strand and the newly produced strand and trusts the old one, removing the newer base and replacing it with the correct match for the older base.
A number of additional biochemical systems are also needed to ensure that normal transcription and replication can go on while these repair systems are doing their job. This is done to make sure that the cells continue about their activities at a normal pace and that biochemical systems don't become intermingled and confused, causing additional errors.
Tolerance systems cope with the difficulties that arise when normal replication is blocked at a damaged site. These enzymes essentially either stop the replication if the site is being repaired and holds off until the repair is done, or it investigates the site with a number of specific enzymes to make a "best guess" as to what the base sequence is in the damaged area. This allows replication and transcription to proceed normally even in the case of genetic error.
Another form of a biochemical assurance system is a retrieval system, which takes care of errors that are still carried over to a daughter molecule, almost as a mirror image or an error checker on a tolerance system. If an error is found, a retrieval system returns to the original sequence and makes a biochemical request that a repair system come immediately to correct the error; once the true structure or sequence is revealed, the enzyme returns to the daughter molecule and inserts the correct sequence or structure.
Together, this network of systems facilitates the ongoing health of our DNA, making sure that our cells can successfully replicate and carry on their day to day tasks in keeping us alive and functional.