Identification of Aptamer for Human Telomeric Repeat Binding Factor (TRF1) for the Control of Telomerase Activity

Identification of Aptamer for Human Telomeric Repeat Binding Factor (TRF1) for the Control of Telomerase Activity

Helen Jung

3 September 2013


With the rise of nuclear and linear DNA, eukaryotes had to overcome the imperfect DNA replicating mechanism that arises from DNA polymerases’ inability to start their own sequence. The advance of telomeres, non-coding DNA sequences at the end of linear DNA, allows the preservation of genetic information in coding sequences of DNA. These telomeres shorten in length as the specific DNA molecule repeats replication, but excessive shortening of telomere can have devastating consequences, such as HHS to be further described below. In response, yeast and mammals maintain their telomere within a certain size range through telomerase activity (de Lange, 2005). The access to each telomeric end is strictly controlled by a telomere nucleoprotein complex, and they guard telomeres against indiscriminate elongation by telomerase or inappropriate modification by DNA damage repair system. Especially, telomeric repeat binding factor (TRF1), a protein within the telomere nucleoprotein complex, negatively regulates telomere length; its over-expression causes telomere shortening while its under-expression results telomere elongation. (Kishi, etal, 2001).

oyeraal-Hreidarsson Syndrome (HHS) is an X-linked genetic disorder that shows abnormalities in telomere length and its maintenance, including defects in RTEL1 (Le Guen, etal, 2013). This condition impedes development and shows symptoms of bone marrow failure and immunodeficiency. Currently, there is no effective treatment for this condition. The objective of this study is to select an aptamer—an oligonucleotide of three-dimensional orientation that is selected to bind to and inhibit a specific target protein—using repetitive talon bead-based selection method. In a previous study, the overexpression of the protein TRF1 has shown strong telomere shortening and damage, whereas under-expression of the protein has shown telomere elongation (Kishi, etal, 2001). Thus, development of an aptamer against TRF1 can provide an outlook for forced TRF1 inactivation. TRF1 inhibition results promoted telomeric repair activities and offers potential aptamer therapeutics to alleviate the symptoms of HHS.

This study specifically aims to identify aptamer against TRF1 protein target and to develop realistic potential therapeutic purposes of this aptamer against HHS. Currently, there is no effective way of identification or remedy for the symptoms. Potential medical applications for HHS will further be investigated.

His-tagged TRF1 protein (Catalog number: 13044-H07B) can be purchased from Sino Biological Inc. (; Phone: 86-400-890-9989). Fifty micrograms, or about 990.01 picomoles, of TRF1 protein cost $290. The molecular weight of the target is 50.5Da. Each round of selection will be performed with about 100 picomoles of TRF1 protein and is expected to cost about $30. The selection is performed using talon beads, which are known to and are used in different laboratory (Stovall, 2013) to select against polyhistidine-tagged targets. These beads are already available in the lab with other necessary equipment without any additional cost.


Target Proposal:

Figure 1. The role of TRF1 in telomerase activity regulation and facilitation during S phase of the cell cycle.

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