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Utilizing Murine Inducible Telomerase Alleles in the Studies of Tissue Degeneration/Regeneration and Cancer
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Alternative paths to telomere elongation.

Jennifer J Lee1, Junyeop Lee1, Hyunsook Lee1

  • 1Department of Biological Sciences & Institute of Molecular Biology and Genetics, Seoul National University, 1 Gwanak-Ro, Gwanak-Gu, Seoul 08832, South Korea.

Seminars in Cell & Developmental Biology
|December 9, 2020
PubMed
Summary
This summary is machine-generated.

Alternative Lengthening of Telomeres (ALT) is a recombination pathway used by some cancers to maintain telomeres. This review explores ALT

Keywords:
Alternative lengthening of telomeres (ALT)Break-induced replication (BIR)Replication stressTelomere maintenance mechanism (TMM)Telomeric recombination

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Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Cellular senescence due to telomere shortening is a key factor in cancer development.
  • Most cancers use telomerase for telomere maintenance, but a subset utilizes the Alternative Lengthening of Telomeres (ALT) pathway.
  • The ALT pathway involves recombination for telomere elongation in cancer cells.

Purpose of the Study:

  • To review current findings on the origins and mechanisms of the ALT pathway.
  • To discuss the factors influencing the choice of the ALT pathway.
  • To explore the epigenetic regulation of telomeres in ALT cancers and potential clinical applications.

Main Methods:

  • Literature review of current research on ALT.
  • Analysis of evidence regarding break-induced replication (BIR) and homologous recombination in ALT.
  • Examination of studies on replication stress and its role in ALT telomere synthesis.

Main Results:

  • Break-induced replication (BIR), often RAD51-independent, is implicated in ALT telomere synthesis.
  • RAD51-dependent homologous recombination is crucial for homology search and inter-chromosomal telomere recombination in ALT cancer maintenance.
  • Replication fork breakdown under replication stress is a proposed trigger for BIR at telomeres in ALT.

Conclusions:

  • ALT is a complex recombination pathway critical for telomere maintenance in a subset of human cancers.
  • Further research is needed to fully elucidate the mechanisms of ALT and its clinical relevance.
  • Understanding ALT offers potential avenues for novel cancer therapies.