dd7086c20dfc4485ec8677f2a66357b8 IntJouMol_a2018v19n1p294.pdf 512d47e36a4a6544bc0935d9d855fc06b590e9ad IntJouMol_a2018v19n1p294.pdf c2bb98775b5d4a08ad78c71990b48211eac6cd557cb7c5397d88d7b1a58a72e2 IntJouMol_a2018v19n1p294.pdf Title: Telomeres: Implications for Cancer Development Subject: Telomeres facilitate the protection of natural ends of chromosomes from constitutive exposure to the DNA damage response (DDR). This is most likely achieved by a lariat structure that hides the linear telomeric DNA through protein-protein and protein-DNA interactions. The telomere shortening associated with DNA replication in the absence of a compensatory mechanism culminates in unmasked telomeres. Then, the subsequent activation of the DDR will define the fate of cells according to the functionality of cell cycle checkpoints. Dysfunctional telomeres can suppress cancer development by engaging replicative senescence or apoptotic pathways, but they can also promote tumour initiation. Studies in telomere dynamics and karyotype analysis underpin telomere crisis as a key event driving genomic instability. Significant attainment of telomerase or alternative lengthening of telomeres (ALT)-pathway to maintain telomere length may be permissive and required for clonal evolution of genomically-unstable cells during progression to malignancy. We summarise current knowledge of the role of telomeres in the maintenance of chromosomal stability and carcinogenesis. Keywords: telomere-dysfunction; chromosome instability; cancer Author: Aina Bernal and Laura Tusell Creator: LaTeX with hyperref package Producer: pdfTeX-1.40.17 CreationDate: Fri Jan 19 09:38:27 2018 CET ModDate: Fri Jan 19 09:38:27 2018 CET Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 21 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 688726 bytes Optimized: no PDF version: 1.5 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- VHLMCD+URWPalladioL-Ital Type 1 Custom yes yes no 86 0 KCSPSB+URWPalladioL-Bold Type 1 Custom yes yes no 87 0 OXBKYU+TeXGyreAdventor-Bold Type 1 Custom yes yes no 88 0 WZJAYO+URWPalladioL-Roma Type 1 Custom yes yes no 89 0 GYREAE+CMSY10 Type 1 Builtin yes yes no 90 0 KORLVE+VnURWPalladioL Type 1 Custom yes yes no 91 0 CKUPDE+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 96 0 IRWHZX+TimesNewRomanPSMT Type 1C 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