Using telomeric chromosomal aberrations to evaluate clastogen-induced genomic instability in mammalian cells
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REVIEW
Using telomeric chromosomal aberrations to evaluate clastogen-induced genomic instability in mammalian cells Alejandro D. Bolzán
Received: 23 July 2020 / Revised: 6 September 2020 / Accepted: 6 September 2020 # Springer Nature B.V. 2020
Abstract Telomeres, the specialized nucleoproteic complexes localized at the physical ends of linear eukaryotic chromosomes, play a fundamental role in maintaining chromosomal stability and integrity, being one of the leading guardians of genome stability. In recent years, the identification and analysis of chromosomal aberrations involving telomeres has proven to be a unique tool to evaluate misrepaired and unrepaired chromosome damage in mammalian cells. Telomere instability constitutes an important source of genomic instability, a phenomenon characteristic of cancer cells, and also common in cells exposed to chemical or physical mutagens which induce chromosomal aberrations by producing chromosome breakage (clastogens). In the present review, we will focus on the chromosomal aberrations involving telomeres and their importance to determine the clastogen-induced genomic instability present in mammalian cells.
Responsible Editor: Beth Sullivan A. D. Bolzán Laboratorio de Citogenética y Mutagénesis, Instituto Multidisciplinario de Biología Celular (IMBICE, CONICET-CICPBA-UNLP), Calle 526 y Camino General Belgrano, B1906APO La Plata, Buenos Aires, Argentina A. D. Bolzán (*) Facultad de Ciencias Naturales y Museo, Universidad Nacional de La Plata, Calle 60 y 122, La Plata, Buenos Aires, Argentina e-mail: [email protected] e-mail: [email protected]
Keywords Telomere . Telomere instability . Chromosomal instability . Chromosome damage . Telomere attrition . Telomere dysfunction Abbreviations BFB Breakage-fusion-bridge CF Compound fragment DDR DNA damage response DSB Double-strand break/s EBV Epstein-Barr Virus HR Homologous recombination IC Incomplete chromosome ICE Incomplete chromosome elements IF Interstitial fragment NHEJ Non-homologous end joining ssDNA Single-stranded DNA SSB Single-strand break/s TF Terminal fragment
Introduction Telomeres (from the Greek, telo = end, and mere = part) are specialized nucleoproteic complexes localized at the physical ends of linear eukaryotic chromosomes that maintain their stability and integrity (Doksani 2019; Maciejowski and de Lange 2017; Shay and Wright 2019). Mammalian telomeres are composed of tandem arrays of the repetitive sequence (TTAGGG)n, associated with a multiprotein complex named “shelterin,” and a class of long non-coding RNA molecules known
A. D. Bolzán
as “TERRA” (Bettin et al. 2019; Maciejowski and de Lange 2017; Schmutz and de Lange 2016; Shay and Wright 2019). Telomeres prevent the ends of linear chromosomes from being recognized as DNA doublestrand breaks (DSB) by the DNA repair machinery, i.e., they mask natural chromosome ends from the DNA damage response (DDR) and repair pathways (Doksani 2019; Maciejowski and de Lange 2017; Shay and Wright 2019). Thus, telomeres protect chromosomes from degradation
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