Aziz Sancar, Paul Modrich, and Tomas Lindahl were rewarded with the nobel chemistry prize in 2015 for exhibiting their DNA repair mechanisms and processes primarily through the use of catalytic properties of enzymes. As the ozone layer has commenced its thinning due to human-induced pollution, not protecting against the sun’s UV ray as efficiently as in the past, it has been underlying the issue with carcinogens residing in humans. Carcinogens are cancer causing agents and these lead to skin cancer, which some of the types can be fatal if not identified early: such as melanoma. The UV rays tend to destroy the folate (or folic acid) in cells, subsequent to destroying the cell’s melanin (this protects the cell’s organelles), which assists in maintaining homeostasis within people’s bodies such as through helping treat anemia, inhibiting carcinogens, and producing reproductive components which provide assistance with reproduction for both men and women. Aziz Sancar, who won the nobel chemistry prize, is a Turkish biochemist and molecular biologist who specializes in DNA repair. He was born on September 8, 1946 and was raised in a small town by the name of Savur within Turkey during his childhood years. Sancar lived in a typical middle class family at the time before he went on to pursue his dreams regarding science and accomplish many things.His greatest accomplishment was when he acknowledged that a photoreactive enzyme, called photolyase, uses blue light energy to fix DNA which has been damaged by the sun’s harmful UV rays, typically being UVB rays which actually penetrate the skin in a malignant manner. Photoreactive enzymes are enzymes which correspond with the chemical action of light itself. He learned this from Dr. Claud S. Rupert, who had conducted his own research regarding DNA repair. First, a pyrimidine is a clear crystalline structure and second, a dimer is a molecule which is comprised of two identical molecules attached or “linked” to each other. It has been perceived that UV rays change two pyrimidines within cells, which must be adjacent to each other (these were specifically adjacent thymines, which are one of the four types of bases of nucleic acids which are basic units which DNA is composed of), in a CPD which is short for cyclobutane pyrimidine dimer. The adjacent thymine bases are still within the CPD but they become distorted due to the UV damage. In 1949, Albert Kelner from Cold Spring Harbor perceived that DNA tends to repair itself subsequent to the damage attributing to the harmful UV light. He came to the conclusion that this repair occurred miraculously if the DNA was exposed to certain light, with no sufficient explanation as for why it took place. Dr. Claud S. Rupert had inquiries and began to research this situation to deepen his understanding. He articulated an explanation as to how DNA repairs itself; by having photolyase enzymes use blue light energy to repair the faulty parts of the DNA strand. But a question was induced: how could photolyase use blue light energy for repair if it is a protein? How is it a photoreactive enzyme since proteins are not able to absorb that sort of light? Numerous chemists attempted to figure out why photolyase is actually able to absorb blue light. Many have been quite unsuccessful due to the fact that it was inconvenient to accumulate these enzymes. Therefore, Rupert looked to an E. Coli cell, a bacteria which resides in humans’ and animals’ intestines, which withholds only approximately 10-20 photolyase molecules. This made it inconvenient and harder to not only isolate the enzyme, but to also purify it to have a further look at it to evaluate why the photolyase is actually able to absorb blue light since it is a protein after all. This is when Aziz Sancar came into play as he worked on the experiment with Rupert. After months of trying, Sancar was able to clone the photolyase enzyme and produce it in abundant amounts to vividly observe and evaluate it. This was as a result of gene cloning becoming a trend at Stanford University in 1974. The purification of the enzyme ensued this event so that only the enzyme itself would be examined. During the purification process, Sancar and his colleagues discovered that the photoreactive enzyme was blue in color itself. It became explicit to them that the blue color of the photolyase depicted that it absorbs blue light, and this was without any chemical analysis. But the search for the light absorbing factors of the photolyase did not end there as the blue color of the enzyme was only a confirmation of its ability to take in blue light. To their astonishment, Sancar and his colleagues discovered that the enzyme has two light absorbing components: methenyltetrahydrofolate (folate) and deprotonated flavin adenine dinucleotide (FADH–). It was anticipated that the folate absorbs the blue light and transfers that light energy to the flavin component (FADH–), which is one of the light absorbing components of the photolyase. The analogy mentioned by Sancar for the folate was that it is like a solar panel; it absorbs light and transfers energy. The flavin was discovered to be a catalyst for the DNA repair process as it will later on be expanded upon. Additionally, this is the reaction mechanism of the photolyase repairing a DNA strand; the photolyase enzyme forms ionic bonds to attach to phosphate remnants of the damaged DNA and incorporates the thymine dimer, within the CPD (as mentioned previously), in the repair process site. Keep in mind that the thymine dimer is distorted due to the UV damage which, again, converted adjacent thymine pyrimidines to a cyclobutane pyrimidine dimer which withholds the distorted thymine molecule. Once the distorted thymine dimer in the CPD is flipped in a way to be integrated in the whole reparation site, the adjacent thymine (still distorted) is now attached to the flavin component of the photolyase through dispersion forces. This reaction, which takes place through the flavin catalyst, takes place as a result of the folate absorbing a photon. The folate, which had already absorbed a blue light photon, transfers the blue light energy to the flavin component of the enzyme and the flavin, through cyclic redox reaction, splits the cyclobutane in the CPD to make the distorted adjacent thymines not be adjacent anymore. A redox reaction consists of a molecule going through both reduction and oxidation. As a result of this, the DNA that is now repaired detaches from the enzyme as the thymine is no longer distorted from the UV rays. The effect of light was shown as Sancar experimented even further. He kept E. coli cells in a room, half of the quantity being contained in the dark and the other half being contained under light. As anticipated, the E. coli under UV light had its adjacent thymines vanish through DNA repair as these E. coli cells were exposed to blue light. The other half of the bacteria, which were not exposed to any sort of light, still had the distorted adjacent thymine dimers present in the CPD. This DNA reparation from blue light led to concept of nucleotide excision repair in which “damaged based are cut out within a string of nucleotides, and replaced with DNA as directed by the undamaged template strand” (bx.psu.edu). In other words, the damaged parts induced by the UV rays are removed from the genome in the bacteria (the genome is the set of haploid chromosomes in the E. coli since bacteria doesn’t contain paired chromosomes). Furthermore, the distorted thymine dimers are now primarily being focused on in nucleotide excision repair. These are symbolized as T<>T. After the removal or excision of the thymine dimers from human DNA or E. coli, the gap in the DNA becomes refilled based off of the synthesis of new DNA. This synthesis takes place based off of the undamaged strand of DNA since DNA is a strand of patterns. A colleague of Sancar believed that the transcription (the process of DNA copying information into a new molecule of RNA, which carries out DNA messages) sped up the process of DNA excision repair. Contrary to what he believed, Sancar and his colleague came to the realization that RNA actually hindered the DNA repair process, to their surprise. They assumed it was due to the fact that RNA may have possibly interfered with proteins which assisted in the synthesis of DNA to replace the gap which thymine dimers were excised or removed from. Thus, a new reparation method for DNA derived from this as Sancar and his colleague purified a protein of 130 kDa which overcame the issue of RNA inhibiting DNA synthesis, and it also helped further cultivate the proteins which were originally aiding in nucleotide excision repair. As a result of this success, Sancar decided to name this protein “transcription-repair-coupling-factor (TRCF). This protein is classified as a translocase protein. Translocases are proteins which help move another molecule around, usually across a membrane. As for the other chemistry nobel prize winner of 2015, Paul Modrich, he also discovered another path for repairing DNA molecules. As Modrich grew up in New Mexico after his father met his mother subsequent to emigrating from Croatia, he noticed that his parents had different perspectives. His mother was always involved in her children’s lives while his father was more of a hands-off type of being, leading to Modrich being a successful independent individual. As he grew older, Modrich grew fond of photography and realized that photography was what lead to him growing even more fond of chemistry and biology because photography aided him in seeing the beauty in the sciences. Thus, he became a profound biochemist with noteworthy achievements.In general, through researching previous experiments, Modrich perceived that some mutations or DNA damage which occurs is the undermethylation of some bases, induced by harmful UV rays. In terms of chemistry, DNA methylation is as stated, “DNA methylation is a process by which methyl groups are added to the DNA molecule. When located in a gene promoter, DNA methylation typically acts to repress gene transcription” (whatisepigenetics.com). By acknowledging this, one can perceive that it is plausible that DNA methylation represses gene transcription due to mutations being the result of excessive gene transcription; for example, cancer occurs due to the excess and ample amount of white blood cells being produced within the human body. And again, this takes place as a result of the abundant amount of gene transcription.He asserted that if an enzyme can be used to perform the repairing of damaged DNA components, then prior to that it can detect where the damage resides. He used E. Coli DNA to make observations and propose theories. The detection of the undermethylation of DNA strands by enzymes typically ensues replication, as human DNA constantly replicates and copies itself. When DNA is replicated, the new strand is unmodified, meaning that it is undermethylated in a transient manner. Shortly after it being unmodified, it becomes methylated, thus, leading it to be modified. To avert further mutations and damage, the initial DNA strand (the unmethylated one) needs to be methylated before the replicated DNA strand becomes methylated and falls out of its transient state. The enzyme which was found, by Modrich, to be able to perform two functions; 1) detect where the DNA mismatch (damage) takes place and 2) to rectify the situation, was essentially found. The enzyme is called GATC endonuclease, GATC simply representing guanine, adenine, thymine, and cytosine. The following process is the nucleotide excision repair process which was introduced earlier in Sancar’s research. Where the DNA mismatch resides, on the original DNA strand which was being replicated, is where the GATC endonuclease makes a single-strand cut through the DNA strand with the purpose of revealing where the damage has been done by the UV rays. This cut conveniently separates the undermethylated areas of the DNA strand from the normal and correct portions of the strand. Moreover, the GATC endonuclease then acts upon its substrate, which is identified to be the undermethylated (damaged) portion of the original DNA strand. The newly formed gap induced by the GATC endonuclease then becomes filled in by typical cellular enzymes, and then DNA ligase plays a role in the repair process. Finally, the ligation (conjoining of two or more DNA strands) of the original DNA strand and the replicated one occurs. Having this repair process take place before the modification of the replicated DNA molecule greatly prevents the furtherance of mutations, which could lead to severe forms of skin cancer through due to UV rays. As an exceptional scientist himself, Tomas Lindahl cultivated his knowledge in a secondary school where many profound students attended. His family consisted of intellectual people as family members from his father’s side, in particular, were professors, scientists, etc. His intellectual background and his own formidable research was all prior to when he won his nobel prize.Tomas Lindahl, another 2015 nobel chemistry prize laureate, questioned the stability of DNA. While he was conducting research on RNA in Princeton University, Lindahl realized that RNA is much less stable than DNA itself. RNA stands for ribonucleic acid, which its main function is to carry instructions from DNA for the synthesis of proteins. Due to the instability of RNA, Lindahl pondered if DNA is quite unstable as well. He realized that, indeed, DNA also inherently has instability since it constantly undergoes many changes. He realized that one chemical downturn regarding a DNA base, cytosine, is that this particular base easily loses its amino group when affected by small and certain environmental factors. When the amino group leaves, that means the cytosine becomes damaged because it later leads to alterations in genetic composition and mutations. Similarly to the previous nobel prize laureates, Lindahl discovered that UV rays function in the situation regarding DNA damage. He asserted that UV ray damage from the sun led to the amino groups leaving the cytosine within DNA strands. The remnants of the damaged cytosine, subsequent to the amino group being a leaving group, always pairs with guanine as cytosine and guanine always pair up in the double-helix structure of DNA strands. Unfortunately, if a guanine base pairs up with a damaged cytosine lacking its amino group, major mutations can occur as DNA gets replicated. The rest of the plot is quite similar to the other laureates, nucleotide excision repair took place yet again. Lindahl discovered a competent bacterial enzyme which would detect and repair the damaged cytosine sites and eventually, where the enzyme absorbed and banished the damaged portions of the DNA strand is where the gaps were filled in by cellular enzymes. In conclusion, the accomplishments of Sancar, Modrich, and Lindahl are formidable due to the fact that they involve the thinning of the ozone layer and UV rays which underlie the issue of cancer. These nobel prizes were awarded in a plausible manner because these chemists were able to propose mechanisms and figure out processes for repairing damaged DNA due to the malignant UV rays protruding from the sun. This is significant because cancer can be prevented or treated in an easier manner if nucleotide excision repairs take place more often in humans. Fatalities can be avoided along with unbeneficial mutations.