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The structure of human telomerase

Protein function relies heavily on its three-dimensional structure. A European study set out to determine the structure of human telomerase.
The structure of human telomerase
Telomeres are repetitive nucleotide sequences located at the termini of linear chromosomes of eukaryotic organisms. They protect chromosomes from shortening or fusing and thus their length is critical for genomic stability and cell viability.

Telomeres are replenished by telomerase, a unique ribonucleoprotein enzyme that is active in cancer cells but is absent from most somatic cells. Telomerase functions by adding tandem repeats of specific nucleotide sequences at the ends of linear chromosomes. The actual ribonucleoprotein complex comprises a 451 nucleotide RNA along with a variety of proteins besides the reverse transcriptase enzyme.

Despite the emerging role of human telomerase in stem cells, aging and cancer, little is known about its structure. The primary objective of the EU-funded HTR (Towards the structural understanding of human telomerase) project was to employ X-ray crystallography to delineate the 3D structure of separate domains of human telomerase and their interaction.

Researchers generated various RNA constructs that included modifications of the human telomerase domains. Attempts were also made to co-crystallise human telomerase in a complex with the spliceosome protein U1A.

Scientists then investigated the detailed atomic structure of the complementary sequence of human telomere repeats. Following extensive efforts, they successfully solved the structure for one such repeat.

Overall, the HTR study emphasised the need for delineating the 3D structure of human telomerase and its DNA binding sequences. Understanding how the different domains of this protein interact in space is central not only for deciphering its activity but also for inhibiting its function in cancer.

Related information

Keywords

Human telomerase, telomere, cancer, RNA, HTR
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