T elomeres H old the K ey to U nderstanding A ging and C ancer Shruti Koti “Junk DNA does exist for a reason.” The term junk DNA is used nowadays to describe any DNA sequence that does not play a functional role in development, physiology, or some other organism-level capacity. However, junk DNA does exist for a reason. Highly repetitive DNA regions may play a role in gene regulation and chromosomal maintenance, while some transposable elements are thought to be remnants of defective viruses that now permanently reside in our genome (Palazzo & Gregory, 2014). A telomere is a special kind of repetitive nucleotide sequence found at each end of a chromatid that plays a role in protecting against degradation. DNA polymerase, the enzyme that carries out DNA replication, can only synthesize new DNA in the 5’ to 3’ direction, so duplication cannot be carried out through the whole length of a chromosome. This is because in eukaryotic DNA replication, an RNA primer is required for each segment of DNA that is being replicated, so a primer cannot be placed at the very end. Thus, in each duplication, the end of the chromosome is shortened (Levy et. al., 1992). Telomeres therefore act as buffers to prevent genes from getting truncated. Over time, due to each cell division event, telomeres get shorter. Eukaryotic cells use the enzyme telomerase to elongate telomeres, but telomerase has not been detected in normal somatic cells. Therefore the typical response of cells to dysfunctional telomeres is to undergo a senescence growth arrest. “In each duplication, the end of the chromosome is shortened.” Biologically, senescence is the phenomenon that occurs when telomeres reach a critically short length, and normal cells irreversibly stop multiplying and acquire a range of altered functions. Evidence suggests that the senescence response evolved as a failsafe mechanism to prevent proliferation of tumor cells, because as telomeres shorten, the chance that an actual gene may get truncated or mutated increases exponentially (Kim et. al., 2002). Therefore it is advantageous to halt the proliferation of these compromised cells rather than risk the multiplication of damaged cells. As senescent cells accumulate, their altered cellular functions may disrupt the surrounding tissue microenvironment crucial for suppressing the growth of oncogenic cells (cells with mutations in genes that have the potential to cause cancer). Figure #1. Cells that pass the senescence barrier may transform into malignant cancer cells. B erkeley S cientific J ournal • W aste • S pring 2015 • V olume 19 • I ssue 2 • 27 B S J In 1953, James Watson and Frances Crick described the structure of DNA and made history. However, just a few years later, a scientist from the other side of the world was conducting research in the field of molecular evolution that would shape our understanding of genetics. Susuma Ohno was born in Korea to Japanese parents in 1928. From a young age, he showed a love for animals, particularly horses, that would eventually take him to veterinary school. But rather than practicing as a vet, Ohno got pulled in a different direction: experimental science. As he was studying the chromosomes of mammals, he noticed that while there was great variation in the number of chromosomes in different species, the amount of chromosomal material (DNA bases) was the same. So whether there were 17 pairs of chromosomes in the creeping vole, or 84 pairs in the black rhinoceros, they shared the same amount of chromosomal material. This was not the case in lower phylogenetic species. Ohno hypothesized that there had been successive doublings of the amount of chromosomal material over evolutionary time, and recognized that most of the DNA in higher organisms did not contain coding sequences. He collectively called these regions ‘junk DNA’ (Beutler, 2002). We have since realized that there must be an evolutionary reason for its existence, but the name stuck.
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Jul 27, 2019
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