DNA repair strategies – overview
DNA is crucial to life. It carries the fundamental blueprint for the proper functioning of a cell. Thus, a damaged DNA could indicate trouble. A mere structural change could lead to the disruption of the genetic code crucial to the building of proteins. Without an apt and prompt DNA repair, mutation arises. Many of these mutations can lead to genomic instability, and ultimately to metabolic dysfunctions, aging, or diseases, such as cancer. DNA repair strategies are of two major classes: (1) the direct reversal of the chemical process that caused the damage and (2) the replacement of damaged nitrogenous bases.1
DNA repair by direct reversal
The integrity of DNA structure must be kept up at all times as much as possible. Otherwise, the cell would not be able to function as it normally would. Inopportunely, DNAs are prone to damage when exposed to certain mutagens, such as radiation and chemicals. Exposure to them could lead to the incorporation of an incorrect nucleotide during DNA replication.1 One way to correct this is through a direct reversal DNA repair mechanism. In this DNA repair strategy, a template is not required and the change is superseded as the original nucleotide is restored.
DNA repair by excision
Damaged DNA may also be repaired by excision. Unlike the first DNA repair mechanism that does not require a template (as described above) DNA repair by excision requires one. DNA is a double helical structure. Because of this, the undamaged DNA strand could be used as a basis when correcting the damaged strand. It is done so by excising and replacing the damaged DNA with new nucleotides. There are three forms of excision repair: (1) base-excision repair (where a single nucleotide change is recognized and subsequently excised by glycosylases), (2) nucleotide excision repair (where multiple base changes are recognized and then cleaved by endonucleases), and (3) mismatch repair (when mismatched bases are later recognized and eventually corrected by excising the error). All these excision repair mechanisms lead to the definitive restoration of the original sequence.1
Recent study on DNA repair
A recent study by a research team from the University of Southern California reported a DNA repair mechanism in fruit fly cells and mouse cells. They likened the mechanism to an emergency responding team. Accordingly, the DNA repair mechanism of the cell includes a team of paramedics (i.e. myosins) that carry damaged DNA to an emergency room (i.e. nuclear pore) located at the periphery of the nucleus. They found that broken DNA strands prompt a series of threads, called nuclear actin filaments, to assemble and form a transient “road” that links to the edge of the nucleus. The myosin (i.e. a protein conveyed to be “walking” because of the presence of “two legs”) treads the road formed by the nuclear actin filaments while it carries the injured DNA strand towards the nuclear pore. The nuclear pore is viewed by the researchers as the emergency room for damaged DNAs since it is where the cell repairs them.2
The cell with its own scheme for DNA repair is indeed remarkable. DNA carries the code that specifies how proteins are made. Without the cell’s innate ability to correct DNA damage, its integrity would be impaired as well. Two major strategies arise: one that rolls the error back to the original and the other that replaces the damage anew based on a template. The recent findings on DNA repair mechanism on fruit flies and mouse cells revealed how remarkable the process already is and how it can pave the way for more highly anticipating research in humans.
— written by Maria Victoria Gonzaga
1 Farrar , S. (2018). Mechanisms of DNA Repair. Retrieved from https://www.news-medical.net/life-sciences/Mechanisms-of-DNA-Repair.aspx
2 University of Southern California. (2018, June 20). The world’s tiniest first responders: ‘Walking molecules’ haul away damaged DNA to the cell’s emergency room. ScienceDaily. Retrieved from www.sciencedaily.com/releases/2018/06/180620170951.htm