Passage
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 the 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.In healthy somatic cells, however, TERT transcription is generally downregulated by the absence of the oncogene c-Myc and the presence of the tumor suppressor protein WT1. When telomerase is suppressed, the resulting critical telomere shortening has been hypothesized to prevent uncontrolled cell proliferation in adult tissues. In cancerous somatic cells, on the other hand, increased telomerase activity is often associated with tumorigenesis. WT1 is frequently absent and c-Myc is frequently overexpressed in these cells, 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
Adapted from Cifuentes-rojas C, Shippen DE. Telomerase regulation. Mutat Res. 2012;730(1-2) :20-7.
-WT1 and c-Myc most likely alter TERT transcription levels by doing which of the following at the TERT gene promoter?

Question

Passage
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 the 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.In healthy somatic cells, however, TERT transcription is generally downregulated by the absence of the oncogene c-Myc and the presence of the tumor suppressor protein WT1. When telomerase is suppressed, the resulting critical telomere shortening has been hypothesized to prevent uncontrolled cell proliferation in adult tissues. In cancerous somatic cells, on the other hand, increased telomerase activity is often associated with tumorigenesis. WT1 is frequently absent and c-Myc is frequently overexpressed in these cells, 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
Adapted from Cifuentes-rojas C, Shippen DE. Telomerase regulation. Mutat Res. 2012;730(1-2) :20-7.
-WT1 and c-Myc most likely alter TERT transcription levels by doing which of the following at the TERT gene promoter?

Quizplus · Accepted Answer

11ecba2d_0ff6_7fe6_a3bf_87c398650c76_MD0008_00 RNA polymerases are responsible for carrying out transcription and must bind DNA at a promoter region for transcription to be initiated. Transcription factors are proteins that can bind to DNA near gene promoter regions and either increase transcription (activators) or decrease transcription (repressors). Activators facilitate RNA polymerase binding to the promoter, and repressors inhibit binding. According to the passage, WT1 is present in cells that do not express TERT (healthy somatic cells) and absent in cells that do express it (cancer cells, somatic and germ cells). The opposite occurs with c-Myc, which is absent in cells that do not express TERT and present in cells that do. The presence of WT1 in healthy somatic cells suggests that it inhibits TERT expression in these cells at the transcriptional level. In contrast, c-Myc most likely promotes TERT expression. Based on this information, WT1 must be acting as a repressor and c-Myc must be acting as an activator. Therefore, WT1 and c-Myc must inhibit and facilitate RNA polymerase binding, respectively. (Choices B and D) DNA polymerase is involved in replication, not transcription. Transcription factors do not affect DNA polymerase binding to DNA. (Choice C) WT1 is a repressor whereas c-Myc is an activator. WT1 inhibits binding and c-Myc facilitates binding, not the other way around. Educational objective: Transcription factors can upregulate or downregulate transcription by influencing the ability of RNA polymerase to bind a promoter. Transcription factors that increase transcription are called activators and facilitate RNA polymerase binding whereas those that decrease transcription are called repressors and inhibit binding.

Passage Each Time a Eukaryotic Cell Replicates Its DNA, the Telomeres