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Reference: Harrington L (2005) Making the most of a little: dosage effects in eukaryotic telomere length maintenance. Chromosome Res 13(5):493-504

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Abstract


Telomerase contains at least two essential components: the telomerase reverse transcriptase (TERT), and the telomerase RNA, which provides the template for the reverse transcription of new telomere DNA by TERT. Loss of telomerase enzymatic function leads to a progressive attrition of telomeric sequence over time, eventually resulting in the disappearance of detectable telomeric DNA and the emergence of chromosome end-to-end fusions, followed by growth arrest or cell death. Recently, the consequences of partial loss of telomerase function have revealed interesting dosage-dependent effects on telomere length and stability. In both mice and humans, hemizygosity for the telomerase RNA or TERT leads to an inability to maintain telomeres; in humans, this insufficiency can lead to diseases such as aplastic anaemia or dyskeratosis congenita. In the budding yeast S. cerevisiae, compound heterozygosity in different telomerase components also results in shortened telomeres. Thus, partial loss of telomerase function can result in a latent but measurable compromise in telomere length. These dosage-dependent effects illuminate a mechanism by which subtle heritable defects in genome integrity can eventually become pernicious.

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Harrington L
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