Alternative Lengthening of Telomeres: Building Bridges To Connect Chromosome Ends

• Published in: Trends in cancer Vol. 6; no. 3; p. 247
• Main Authors: Hoang, Song My, O'Sullivan, Roderick J
• Format: Journal Article
• Language: English
• Published: United States 01.03.2020
• Subjects: Chromatin - ultrastructure; Clonal Evolution; Co-Repressor Proteins - antagonists & inhibitors; Co-Repressor Proteins - physiology; DNA Damage; DNA Repair; DNA Replication; DNA, Neoplasm - metabolism; DNA, Neoplasm - ultrastructure; Histones - physiology; Homologous Recombination; Humans; Models, Genetic; Molecular Chaperones - antagonists & inhibitors; Molecular Chaperones - physiology; Mutation; Neoplasm Proteins - antagonists & inhibitors; Neoplasm Proteins - genetics; Neoplasm Proteins - physiology; Neoplasms - genetics; Neoplasms - ultrastructure; Nucleic Acid Conformation; Telomerase - genetics; Telomerase - physiology; Telomere Homeostasis; X-linked Nuclear Protein - antagonists & inhibitors; X-linked Nuclear Protein - physiology; cancer; homology-directed repair; DNA damage; replicative stress; telomere
• ISSN: 2405-8025
• DOI: 10.1016/j.trecan.2019.12.009

Alternative lengthening of telomeres (ALT) is a mechanism of telomere maintenance that is observed in many of the most recalcitrant cancer subtypes. Telomeres in ALT cancer cells exhibit a distinctive nucleoprotein architecture shaped by the mismanagement of chromatin that fosters cycles of DNA damage and replicative stress that activate homology-directed repair (HDR). Mutations in specific chromatin-remodeling factors appear to be key determinants of the emergence and survival of ALT cancer cells. However, these may represent vulnerabilities for the targeted elimination of ALT cancer cells that infiltrate tissues and organs to become devastating tumors. In this review we examine recent findings that provide new insights into the factors and mechanisms that mediate telomere length maintenance and survival of ALT cancer cells.