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DNA Repair[change | change source]
DNA repair refers to a set of processes by which cells fix errors in their DNA. These errors are caused by things outside of the cell like UV light and radiation or by natural processes in the body.[1] Cells are always repairing their DNA. When a cell cannot repair its DNA, bad things, such as harmful mutations or cell death, can happen.[2] Sometimes, cells can still live with damaged DNA and are able to pass down the error to future cells.
Sources of damage[change | change source]
DNA damage happens all the time. 1,000 to 1,000,000 errors can happen in only one day.[3] There are many things that cause damage, such as:
1. Ultraviolet radiation from the sun[4]
2. Radiation from things besides the sun, like x-rays
3. Certain poisons made by plants[5]
4. Certain man-made chemicals[6]
Sometimes, DNA damage is caused by things inside the body as well. For example, metabolic activities in the liver or stomach can make chemicals that cause damage.
Types of damage[change | change source]
DNA is structured as a double helix made from two chains of nucleotide bases. The four main forms in which these chains are damaged are:
1. When one base is damaged or paired incorrectly
2. When more than one base is damaged or paired incorrectly
3. When one DNA strand breaks
4. When both DNA strands break[8]
How damage is fixed[change | change source]
DNA stores the genetic code of a cell in a sequence of base pairs. This code tells the cell which proteins it needs to make. DNA damage can make the code unreadable, sometimes in areas that code for proteins needed by the cell. To keep everything running smoothly, the cell uses several methods to fix DNA damage. There are four main ways by which cells repair DNA: mismatch repair, base excision, nucleotide excision repair, and DNA damage bypass.
Mismatch repair[change | change source]
DNA strands are complementary to one another. The bases on one strand must match with the bases on the other strand. For example, if an adenine base is on one strand, then it must pair with the thymine base on the other strand. For more information, see complementarity.
Sometimes, DNA damage causes a base to pair up with the wrong base. For example, adenine could pair with cytosine instead of thymine. To fix this, the cell cuts the error-containing DNA out of the strand. Then, it uses the complementary strand of DNA as a template to make a new, correct strand. After the new strand is made using DNA polymerase, the strand is connected to the DNA helix with DNA ligase.[9]
Base excision[change | change source]
Base excision is when a cell fixes a single damaged base. Sometimes, a base has substituents (groups of atoms) added to or missing from it. The cell has many enzymes that look for bases damaged in this way. When it finds one, the enzyme will remove the nitrogen section from the DNA base but will leave the sugar backbone. This will leave a hole in the DNA strand.[10]
Cells fill this hole using AP repair. AP repair is when an enzyme removes the sugar backbone out of the DNA. Then, DNA polymerase fills the hole with the correct base.[11]
Nucleotide excision repair[change | change source]
Nucleotide excision repair is when a cell removes a large piece of damaged DNA and remakes it in the correct form.[12] Nucleotide excision repair is like base excision, as enzymes must look through the DNA strand for errors. However, when an error is found, the cell will remove a larger piece of DNA than in base excision. After, DNA polymerase remakes the strand, using the complementary strand as a model. Nucleotide excision repair is important because it can fix many types of DNA damage. This is also the main way in which damage from UV light is fixed.[11]
DNA damage bypass[change | change source]
Sometimes, a cell cannot repair the damage in its DNA. Still, cells can avoid passing on the error to future cells through DNA damage bypass. [11] When a cell gets ready for mitosis, where a single cell separates into two new cells, the cell copies all of its DNA. The new DNA is split between the two new cells. In DNA damage bypass, the cell skips over damaged areas when copying its DNA. As a result, the new DNA has a hole where the damaged DNA was not copied. The cell fills the hole by taking the matching section of the original DNA and putting it into the new DNA strand. The hole left in the original DNA is then filled using DNA polymerase.[13]
References[change | change source]
- ↑ Ohta T, Tokishita S, Mochizuki K, Kawase J, Sakahira M, Yamagata H. 2006. UV Sensitivity and Mutagenesis of the Extremely Thermophilic Eubacterium Thermus thermophilus HB27. Genes and Environment 28 (2): 56–61. doi:10.3123/jemsge.28.56.
- ↑ Acharya, PV. 1971. The isolation and partial characterization of age-correlated oligo-deoxyribo-ribonucleotides with covalently linked aspartyl-glutamyl polypeptides. Johns Hopkins Medical Journal. Supplement (1): 254–60.
- ↑ Lodish H, Berk A, Matsudaira P, Kaiser CA, Krieger M, Scott MP, Zipursky SL, Darnell J. 2004. Molecular Biology of the Cell, p963. WH Freeman: New York, NY. 5th ed.
- ↑ Peak, M. J. and Peak, J. G. 1991. Effects of Solar Ultraviolet Photons on Mammalian Cell DNA. Biological and Medical Research Division, Argonne National Laboratory.
- ↑ Bhaskar ASB, Gupta N, Rao PVL. 2012. Transcriptomic profile of host response in mouse brain after exposure to plant toxin abrin. Toxicology. 299(1):33-43. DOI: 10.1016/j.tox.2012.05.005.
- ↑ Acharya, PV Narasimh; Irreparable DNA-Damage by Industrial Pollutants in Pre-mature Aging, Chemical Carcinogenesis and Cardiac Hypertrophy: Experiments and Theory; 1st International Meeting of Heads of Clinical Biochemistry Laboratories, Jerusalem, Israel. April 1977.
- ↑ Roulston A, Marcellus RC, Branton PE (1999). "Viruses and apoptosis". Annu. Rev. Microbiol. 53: 577–628. doi:10.1146/annurev.micro.53.1.577
- ↑ McKinnon, PJ and Caldecott, KW. 2007. DNA strand break repair and human genetic disease. Annual Review of Genomics and Human Genetics. (8):37-55. DOI: 10.1146/annurev.genom.7.080505.115648
- ↑ Iyer R, Pluciennik A, Burdett V, Modrich P (2006). "DNA mismatch repair: functions and mechanisms". Chem Rev 106 (2): 302–23. doi:10.1021/cr0404794
- ↑ Liu Y, Prasad R, Beard WA, Kedar PS, Hou EW, Shock DD, Wilson SH, (2007). "Coordination of Steps in Single-nucleotide Base Excision Repair Mediated by Apurinic/Apyrimidinic Endonuclease 1 and DNA Polymerase β". Journal of Biological Chemistry 282 (18): 13532–13541. doi:10.1074/jbc.M611295200
- ↑ 11.0 11.1 11.2 Hartl, D. 2011. Essential Genetics: A Genomics Perspective. Jones and Bartlett Publishers, LLC.
- ↑ Truglio, JJ, Croteau DL, Van Houten B, Kisker C. 2006. Prokaryotic Nucleotide Excision Repair: The UvrABC System. Chemical Reviews 106 (2): 233–252. doi:10.1021/cr040471u
- ↑ Yang, W. 2011. Surviving the sun: Repair and bypass of DNA UV lesions. Protein Science. (20)11:1781-1789. DOI: 10.1002/pro.723.