This page was produced as an assignment for an undergraduate course at Davidson College.


A SOLUTION TO THE "END-REPLICATION" PROBLEM  (click here for a review of DNA replication)



Figure 1: Telomerase Structure at Work.  The telomerase enzyme complex consists of an RNA component and a protein component.  The protein component's catalytic subunit acts as a reverse transcriptase (green), using telomerase RNA (blue/white) as a template for the addition of telomeric repeat sequences to the telomere DNA strand (red).
Source: Thomas Cech


(click picture to see larger image)

Figure 2: Amino acid sequence of human TP2.   (a) Predicted amino acid sequence of human TP2.  Homology to the reverse transcriptase domain is boxed with a solid line.   (b) Domain of highest homology between TP2 (human telomerase catalytic subunit), p123 (ciliate Euplotes aediculatus ~123 kDa telomerase catalytic subunit), and Est2 (yeast Saccharomyces cerevisiae homologous telomerase-associated subunit).  Residues conserved in at least two of the aligned proteins are shown in boldface type.  Residues conserved among reverse transcriptase are boxed, with consensus residues shown below.
Source: Harrington et al, December 1997

(click picture to see larger image)

Figure 3: Amino Acid Sequence of Human TP1.  (a) Four amino-terminal repeats are indicated by solid lines over the sequence (R1 to R4).  Boxed regions show homology to Tetrahymena p80.  The complete human and murine TP1 sequences have been deposited with GenBank (accession numbers U86136 and U86137, respectively).   (b) (Top) The TP1 amino acid sequence is depicted schematically, with boxed regions as follows: amino-terminal repeats 1 to 4 (R1-R4); gray boxes (1 to 3) show regions of homology between TP1 and Tetrahymena p80.  (Bottom) Human (Hu) and murine (Mu) TP1 amino acid sequences were aligned to Tetrahymena p80; Tetrahymena (Te) sequences identical to either human or mouse at each position are shown in boldface. The underlined, 90-amino acid segment in region 2 contains 46% identity between p80 and human TP1.
Source: Harrington et al, January 1997



 a                 b

Figure 4: A Comparison of Human and Yeast/Ciliate Telomerase RNA.  Vertebrate/human telomerase RNA (a) and yeast/ciliate telomerase RNA (b) differ greatly in sequence and structure, but they share a 5' pseudoknot area close to the template sequence (i.e. the portion used to generate the telomere).
Source: (a) Rfam 3.0 Telomerase-vert    
            (b) Rfam 3.0 Telomerase-cil






Figure 5: TERT Expression in Colonic Tumorigenesis.  (a) Normal colon with low-level hybridization to epithelial cells located primarily in the proliferative zone near the base of crypts.  (b) Increased expression in adenomatous epithelium (right), normal mucosa is on the left.  (c) Increased expression in carcinoma in situ (bottom) arising in an adenomatous polyp.  (d) Strong expression in colon carcinoma metastatic to liver.
Source: Kolquist et al





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