Telomere

The telomeres ( gr τέλος telos " end " and μέρος meros "part" ) are composed of repetitive DNA and associated proteins ends of chromosomes. The repeated sequence ( repeat sequence ) and by this repetition (Repeat frequency) induced length here are different in different organisms. In vertebrates, the sequence TTAGGG is repeated thousands of times, and accordingly several kilobase pairs long. Telomeres are essential for the stability of chromosome structural elements of DNA. For the stabilizing effect and the folded secondary structure of telomeres is essential.

Structure of telomeres

The exact spatial structure of telomeres is not yet finally resolved. It depends on the base sequence, so that can involve several binding motifs occur.

In higher eukaryotes, we find a typical thymine and guaninreiches motif in which one assumes that it forms a quadruple helix. Here, first pairs of the 3'- strand overlapping with itself and forms abnormal GG double bonds from. This double strand is paired again with itself and forms a quadruple helix, which receives them guanines called Hoogsteen bonds.

This DNA sequence is recognized and bound by specific DNA-binding proteins. This protein complex is responsible for enabling the cell to differentiate the natural chromosome end of unwanted DNA strand breaks.

Telomeres during replication

With each cell division, telomeres are shortened, since the DNA polymerase on the lagging strand can not start. Falls below a critical minimum telomere length of approximately 4 kbp, the cell can no longer divide on. Often occurs, the programmed cell death ( apoptosis) or a permanent growth arrest one ( senescence ). The limitation resulting from the inability of cellular life is understood as a tumor suppressor mechanism. The enzyme telomerase ( an RNA -protein complex with a reverse transcriptase activity ) can compensate for the shortening again. For this purpose, it adds to the 3'- OH end of G- rich repeat units whose RNA template is in the telomerase itself. Then the leading strand folds down and forms with itself abnormal GG base pairings. From this point, RNA primase, and the DNA polymerase can also result strand ( reverse strand, or also called a discontinuous strand ) fill. Cells in which this enzyme is active, you can share much more common than other body cells. However, the active telomerase is basically single-celled eukaryotes (protozoa ), at higher multicellular organisms only in very specific cells:

• In cells of the germ line,
• In cells that have to share very common as the stem cells ( eg, bone marrow stem cells) or the immune cells, as well as
• Up to 94% of the proliferating cancer cells.

However, it has been shown in knock- out mice that they can remain viable for several generations without telomerase. It is assumed that the repair of the telomeres can vonstattengehen via recombination; clarified this is not but.

Importance

The importance of chromosome ends for its stability first realized the American Nobel laureate Barbara McClintock and Hermann Joseph Muller, who also coined the term telomere (Greek for end- part). Telomeres are associated with biological processes in connection associated with the aging of cells ( cell senescence ), as well as their immortalization, and thus the development of cancer.

The enzyme activity of telomerase can be determined by the TRAP method.

Or G ( 2-3) (TG ) ( 1-6) T (consensus )

Fiction

1999 wrote the American author John Darnton a novel about the topic telomeres in his best-selling twin park (page 244 ff ) ( The Experiment ).