Molecular Genetics

The structure that is the telomere is made by reverse transcription.

Facts

In early experiments, recessive mutations in two complementation groups result in the progressive shortening of telomeres. An enzyme, named telomerase, was isolated from Oxytrichia. It catalyzes the addition of TTGGGG to telomeres. It can work on all possible ends (GT, GTT, GTTG ...GTTGGGG) The enzyme contains an RNA, called a guide RNA. This RNA contains the 6 bp CCCCAA template sequence in a 9bp complementary region.

During many generations of cell replication the length of telomeres gradually increases (7 to 10 bp/generation in Trypanosoma brucei). The steady lengthening is followed by sudden reductions in length. Immortalized tissue culture cells have higher levels of telomerase than cells in primary cultures.

Interpretations

• Post-DNA replication addition of telomere repeats to the ends of chromosomal DNA resolves the telomere paradox.
• The telomere DNA polymerase is a reverse transcriptase (RNA-dependent).
• That the complementary sequence in the guide RNA is longer than one repeat causes tandem repetition in telomeres.

Further information

• Telomerase reverse transcriptases contain amino acid sequence motifs similar to those of other reverse transcriptatses.
• The cause of catastrophic losses of telomere length are unknown.
• In Saccharomyces cerevisiae, three genes, in addition to the gene for the telomerase enzyme, are required to prevent the telomeres from getting continuously shorter. A frameshift is required during translation of the mRNA of one of these genes.
• Progressive shortening of telomeres may be a mechanism of aging and can lead to tumor formation, particularly when DNA repair processes are impaired (ref). Chromosome rearrangements are frequent, probably due to breakage-fusion-bridge cycles (ref).
• Recent reviews on telomere synthesis and structure are available.
• More information is available on the web.
• Sequences immediately internal to telomeres (telomere-associated sequences) also play important roles.
• More recently, further genes needed for telomere function have been identified. They include four for subunits of the telomerase protein component (ref), one for the RNA and several for telomere binding proteins important for function (ref).

This is page 1353 of Molecular Genetics by Ulrich Melcher, © 1997, 1998, 1999, 2001