Each time a eukaryotic cell replicates its DNA, the telomeres at the ends of each chromosome become slightly shorter.  When telomeres reach a critically short length, the cells enter a senescent state, in which cell division ceases (Figure 1).  In humans, conditions such as hypertension, liver disease, and Alzheimer disease have been associated with the decreased telomere length and resulting senescence that occur as part of the normal aging process.Figure 1Cells that must be able to divide indefinitely (stem cells and germ cells) express an enzyme known as telomerase.  Functional telomerase consists of a protein subunit called telomerase reverse transcriptase (TERT) and a noncoding RNA subunit called telomerase RNA (TR).  Using a portion of TR as a template, telomerase extends telomeres by continuously adding the sequence 5′-TTAGGG-3′ to the ends of chromosomes.  The complement strand is then filled in by DNA polymerase.  Telomere extension allows these cells to avoid senescence.However, in healthy somatic cells telomerase expression is suppressed, and the resulting critical telomere shortening has been hypothesized to prevent uncontrolled cell proliferation in adult tissues.  Increased telomerase activity is often associated with tumorigenesis.  TERT transcription is generally controlled by chromatin structure as well as the oncogene c-Myc and the tumor suppressor protein WT1.  Healthy cells express relatively high levels of WT1 and low levels of c-Myc whereas cancerous cells often express low levels of WT1 and high levels of c-Myc, leading to increased TERT expression.In addition to transcriptional control, TERT can be regulated at the post-transcriptional level.  The TERT gene consists of 16 exons and 15 introns that can be spliced into more than 20 different isoforms in humans.  Only one isoform (the active isoform) is known to extend telomeres.  However, the i2 isoform, in which intron 2 is partially included in the mature mRNA (Figure 2), has been hypothesized to downregulate residual TERT activity in somatic cells.Figure 2 Question 11Given that in healthy somatic cells the TERT gene is rarely transcribed, where in the chromosomes of these cells is the gene most likely found?A.In a relatively open, uncoiled portion of the chromosomeB.In the portion of the chromosome that binds the kinetochoreC.In a portion of the chromosome that associates with ribosomesD.In a portion of the chromosome that is tightly wound around histones