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.

Emerging roles of telomeric chromatin alterations in cancer / Cacchione, Stefano; Biroccio, Annamaria; Rizzo, Angela. - In: JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH. - ISSN 1756-9966. - 38:1(2019), pp. 1-12. [10.1186/s13046-019-1030-5]

Emerging roles of telomeric chromatin alterations in cancer

Cacchione, Stefano
Primo
Writing – Original Draft Preparation
;
2019

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.
2019
ALT; Cancer; Chromatin; Epigenetics; Heterochromatin; Sirtuins; Telomere; Oncology; Cancer Research
01 Pubblicazione su rivista::01a Articolo in rivista
Emerging roles of telomeric chromatin alterations in cancer / Cacchione, Stefano; Biroccio, Annamaria; Rizzo, Angela. - In: JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH. - ISSN 1756-9966. - 38:1(2019), pp. 1-12. [10.1186/s13046-019-1030-5]
File allegati a questo prodotto
File Dimensione Formato  
Cacchione_Emerging_2019.pdf

accesso aperto

Tipologia: Versione editoriale (versione pubblicata con il layout dell'editore)
Licenza: Creative commons
Dimensione 1.01 MB
Formato Adobe PDF
1.01 MB Adobe PDF

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1219401
Citazioni
  • ???jsp.display-item.citation.pmc??? 18
  • Scopus 26
  • ???jsp.display-item.citation.isi??? 27
social impact