A density map and atomic model of human telomerase holoenzyme are shown in two different views. The scheme of the hTR RNA is shown below the figure. There areserved motifs highlighted by different colors. The colors of the elements are the same as in the past. The t-PK, TWJ and H/ACA are marked. Solid lines and dots are shown for the non-canonical interactions. Credit is given by the DOI: 10.1038/s41422-021-0
A telomere is a region of repetitive nucleotides that are associated with specialized proteins located at the ends of chromosomes to protect them from degradation. The number of times a cell can divide is limited by the shortening of the telomeres. Telomers are related to cell aging. The telomerase will be activated during cell division to synthesise the telomere DNA.
A research group led by Prof. Li Guohui from the DICP of the Chinese Academy of Sciences collaborated with two other groups. Their study was published in Cell Research.
Human telomerase only needs a three-base-paired primer-template duplex to sustain its activity, while the canonical reverse transcriptase requires at least six base pairs. The mechanism of the above phenomenon is not clear.
The human telomerase holoenzyme with bound telomeric DNA has a cryo-EM structure of 3.54 and 3.94 for the catalytic core and the biogenesis module, respectively.
This study shows that the key amino acid Leu980 in the human telomerase plays a key role in controlling the length and pair of the double helix. The researchers found that Leu980 acted like a head, which separated the substrates and only maintained the three-base-paired primer-template duplex.
The studies showed that a tighter six-base pair of the hybrid double was restored by the Leu980 to Glymutation. The Leu980Glymutation would affect the telomerase's ability to synthesise.
The work provides new insights into the synthesis of the telomere repeat.
Futang Wan et al., Zipper head mechanism of telomere synthesis by human telomerase, Cell Research, is more information. There is a DOI of 10.1038/s41422-021-00584-7.
Cell research journal information.
The scientists revealed the mechanism of the telomere synthesis by human telomerase.
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