Telomere dysfunction and genome instability

Cristina Frias, Judit Pampalona, Anna Genesca, Laura Tusell

Research output: Contribution to journalReview articleResearchpeer-review

38 Citations (Scopus)

Abstract

The nucleoprotein complexes that cap the very ends of the eukaryotic chromosomes, named telomeres, are indispensable for cell viability. Telomeric DNA shortens in each cell division until it cannot exert end-protective functions in human somatic cells. Additionally, several proteins have been described to play a key role in telomere homeostasis preventing chromosome extremities to be recognized as double-stranded breaks. When telomeres become dysfunctional, either through excessive shortening or due to defects in the proteins that form its structure, they trigger p53/pRb pathways what limits proliferative lifespan. Impairment of telomere function together with a compromised senescence/apoptosis response leads to chromosome instability. Fusions between dysfunctional telomeres or even between dysfunctional telomeres and double-stranded breaks can initiate breakage-fusion-bridge cycles. Initially, telomere fusions were proposed to cause only structural abnormalities. Nevertheless, changes in chromosome number have also emerged as a possible consequence of alterations in end capping. Here we review the main aspects of telomeres and telomere-based chromosome instability, highlighting why they have been proposed as a driving force for tumourigenesis.
Original languageEnglish
Pages (from-to)2181-2196
JournalFrontiers in Bioscience
Volume17
Issue number6
DOIs
Publication statusPublished - 1 Jun 2012

Keywords

  • Anaphase-bridges
  • Aneuploidy
  • BFB cycles
  • Chromosome instability
  • DNA damage response
  • DSBs
  • Review
  • Telomeres

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