What Is The Alternative Lengthening Of Telomeres - 900 Words

DNA replication results in the gradual shortening of telomeres over time, leading to the activation of senescence or apoptosis. Therefore, telomere length is a key biological signal to limit the indefinite proliferation of somatic cells (Roumelioti, et al., 2016). However, cancer cells can overcome telomere shortening by synthesising a new telomeric DNA from an RNA template through the expression of telomerase (Roumelioti, et al., 2016). Alternatively, 10-15% of human cancers utilise a DNA template in a homology-directed synthesis mechanism called alternative lengthening of telomeres (ALT) (Cesare Reddel, 2010). However, the process by which DNA damage such as telomeric shortening results in the execution of homology-directed synthesis,†¦show more content†¦However, ATR, Rad51 and Hop2 were not required for break-induced telomere synthesis in ALT cells and in fact, knockdown of each gene increased the levels of nascent telomeres. To further support their findings, Dilley an d colleagues studied VA13 HOP2 CRISPR clones lacking Hop2 protein expression and found that no telomere shortening took place. From these findings, the authors could therefore propose that break-induced telomere synthesis and ALT telomere maintenance can occur independently of Rad51-Hop2 and ATR. Dilley and co-workers subsequently determined that the replicative DNA polymerase Pol , including POLD3, POLD4 and POLD1 subunits, were instead required for break-induced telomere synthesis. Whereas Pol , Pol -primase and MCM2-7 replicative helicase were found to be nonessential and were recruited at far lower levels. The POLD3 subunit is also part of the Pol ÃŽ ¶ complex involved in translesion synthesis. However, the REV3L catalytic subunit of Pol ÃŽ ¶ was not required for break-induced telomere synthesis, suggesting POLD3 primarily acts through Pol . This major role of POLD3 has been supported in studies that revealed POLD3 depletion resulted in decreased frequency of replicated ALT telomeres (Roumelioti, et al., 2016). Overall, the results by Dilley et al led to the suggestion that an alternative replisome is required for ALT telomere synthesis. Having proven that Pol is dominantly recruited to TRF1-FokI damage sites, Dilley et al set outShow MoreRelatedScientific Literature Focused On Chromosomal Dna And Dna, Blood Leukocytes, Sputum, And Buccal Cells2398 Words   |  10 PagesChromosomal Telomere Length (TL) In Blood Leukocytes, Sputum, and Buccal Cells as It Relates to Cancer Occurrences by: Andy Barajas Bio 490, Fall 2014 Department of Biological Sciences California State Polytechnic University, Pomona Abstract This is a conglomeration of scientific literature as it relates telomere length in blood cells to the occurrence of cancer. Telomeres are composed of repeating TTAGGG nucleotides and they are found at the ends of chromosomes. These chromosomal caps are what protect