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Telomeres and Telomerase02:41

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In eukaryotic DNA replication, a single-stranded DNA fragment remains at the end of a chromosome after the removal of the final primer. This section of DNA cannot be replicated in the same manner as the rest of the strand because there is no 3’ end to which the newly synthesized DNA can attach. This non-replicated fragment results in gradual loss of the chromosomal DNA during each cell duplication. Additionally, it can induce a DNA damage response by enzymes that recognize single-stranded...
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Utilizing Murine Inducible Telomerase Alleles in the Studies of Tissue Degeneration/Regeneration and Cancer
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Telomerase reverse transcriptase moonlights: Therapeutic targets beyond telomerase.

Yoshiko Maida1, Kenkichi Masutomi1

  • 1Division of Cancer Stem Cell, National Cancer Center Research Institute, Tokyo, Japan.

Cancer Science
|September 3, 2015
PubMed
Summary

Telomerase reverse transcriptase (TERT) has non-canonical functions beyond telomere maintenance, including gene silencing and stem cell regulation. These novel TERT activities represent promising new targets for anticancer therapies.

Keywords:
RNA-dependent RNA polymerasesplice variantsstem celltelomerasetelomerase reverse transcriptase

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Area of Science:

  • Molecular Biology
  • Cancer Research
  • Genetics

Background:

  • Telomeres protect chromosome ends but shorten with cell division, triggering senescence.
  • Telomerase, particularly its catalytic subunit telomerase reverse transcriptase (TERT), maintains telomere length.
  • TERT is highly expressed in cancer cells, making it a target for cancer therapy.

Purpose of the Study:

  • To review the non-canonical functions of TERT beyond its role in telomere maintenance.
  • To explore the potential of these non-canonical TERT functions as therapeutic targets for cancer treatment.

Main Methods:

  • Literature review of recent studies on TERT functions.
  • Analysis of TERT's RNA-dependent RNA polymerase (RdRP) activity.
  • Investigation of TERT's role in gene silencing and stem cell regulation.

Main Results:

  • TERT exhibits functions independent of telomere maintenance, such as regulating gene silencing and heterochromatic transcription via RdRP activity.
  • A distinct TERT-containing complex, separate from the telomerase complex, is involved in cancer stem cell functions.
  • Some TERT splice variants lacking catalytic domains retain non-canonical functions.

Conclusions:

  • TERT possesses significant non-canonical functions that are crucial for processes like stem cell maintenance and gene regulation.
  • Targeting these non-canonical TERT functions offers a novel and potentially more effective strategy for anticancer drug development.