Emerging roles of telomeric chromatin alterations in cancer

Stefano Cacchione, Annamaria Biroccio, Angela Rizzo

Research output: Contribution to journalReview articlepeer-review

Abstract

Telomeres, the nucleoprotein structures that cap the ends of eukaryotic chromosomes, play important and multiple roles in tumorigenesis. Functional telomeres need the establishment of a protective chromatin structure based on the interplay between the specific complex named shelterin and a tight nucleosomal organization. Telomere shortening in duplicating somatic cells leads eventually to the destabilization of the telomere capping structure and to the activation of a DNA damage response (DDR) signaling. The final outcome of this process is cell replicative senescence, which constitute a protective barrier against unlimited proliferation. Cells that can bypass senescence checkpoint continue to divide until a second replicative checkpoint, crisis, characterized by chromosome fusions and rearrangements leading to massive cell death by apoptosis. During crisis telomere dysfunctions can either inhibit cell replication or favor tumorigenesis by the accumulation of chromosomal rearrangements and neoplastic mutations. The acquirement of a telomere maintenance mechanism allows fixing the aberrant phenotype, and gives the neoplastic cell unlimited replicative potential, one of the main hallmarks of cancer. Despite the crucial role that telomeres play in cancer development, little is known about the epigenetic alterations of telomeric chromatin that affect telomere protection and are associated with tumorigenesis. Here we discuss the current knowledge on the role of telomeric chromatin in neoplastic transformation, with a particular focus on H3.3 mutations in alternative lengthening of telomeres (ALT) cancers and sirtuin deacetylases dysfunctions.

Original languageEnglish
Article number21
JournalJournal of Experimental and Clinical Cancer Research
Volume38
Issue number1
DOIs
Publication statusPublished - Jan 17 2019

Keywords

  • ALT
  • Cancer
  • Chromatin
  • Epigenetics
  • Heterochromatin
  • Sirtuins
  • Telomere

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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