Error-Free Repairing Mechanisms
What happens to damaged DNA and how can it be fixed? To answer this question there are many types of mechanisms that the cells within various organisms such as bacteria, humans and even plants may experience. These damages can be caused by ionizing radiation, UV light, mutagens, replication error etc.
One of the first repair mechanisms that will be discussed is direct reversal of damaged DNA which is known to be the most energy efficient. A common type of direct reversal caused by UV light is a product of mutagenic photodimer, cyclobutane pyrimidine dimer (CPD). CPD can be repaired by a mechanism known as photoreactivation whereCPD photolyase, an enzyme that binds to the photodimer and splits the cyclobutane pyrimidine.
Another repair mechanism relevant after DNA proofreading has been completed is base-excision repair which is a type of homology dependent repair system. Homology dependent repair systems are important because they rely on excising a segment of damaged DNA and replacing it with a newly synthesized DNA molecule that complements the strand being repaired. Base-excision repair has the ability to remove incorrect or smaller damaged bases. First, DNA glycosylase recognizes the damage, and cleaves the base-sugar bonds to form apurinic or apyrimidinic (AP) sites. Next, AP endonuclease nicks the damaged section upstream of the AP site. Then, deoxyribophosphodiesterase removes a segment of DNA in order for DNA polymerase to add new nucleotides that complements the other strand. Finally, DNA ligase reconnects the nicks into the backbone.
Nucleotide-excision repair (NER) repairs minor damages in both prokaryotes and eukaryotes that are mainly caused by UV light. NER has the ability to lessen replication and transcription blocks and also fix the minor damages. NER requires a full set of proteins that in order to perform the four stages during this repair process. There are two types of repair mechanisms for NER: Global genomic repair (GGR) and transcription-coupled NER (TC-NER). In GGR, the damaged base is caused by the heterodimeric complex and is recognized. Next, CSA and CSB proteins binds to this damaged site which recruits the multi-protein complex that includes TFIIH. Then, helicases unwind the DNA with single-stranded binding protein allowing it to stabilize its position, and the damaged bases are cleaved and excised. As a result, the damaged bases are repaired by synthesizing and ligating the new DNA. This process is similar to transcription-coupled NER except that RNA polymerase recognizes and binds to CSA and CSB at the site of stalled transcription complex. After TFIIH binds, RNA polymerase, CSA and CSB dissociates from the complex. Such diseases that result from mutation in NER include xeroderma pigmentosum and Cockayne syndrome.
The last repair mechanism is mismatch repair which is responsible for correcting the additional errors that were not corrected by the proofreading function of DNA polymerase. It also has the lowest error rate in the course of replicating DNA. There are three important tasks that mismatch repair systems must undergo. First is to recognize mismatched base pairs. next it needs to determine which base is the incorrect base that was misplaced in the DNA. Finally, it needs to excise the incorrect base and continue to repair the mutation.
The mismatch repair pathway starts off when MutS recognizes the mismatch pair on the newly replicated DNA. Then it recognizes the methylated parent strand and nicks the daughter strand which contains the mismatch base. Because of these repair systems, the probability of having replication error is lowered.
As a result, DNA is only repaired and not replaced in organisms. However, if these repair systems do successfully correct the altered DNA bases, then major inherited diseases will result in future generations during replication.