title: Telomere length, telomeric proteins and genomic instability during the multistep carcinogenic process.
abstract: Telomeres form specialized structures at the ends of eukaryotic chromosomes, preventing them from being wrongly recognized as DNA damage. The human telomere DNA sequence is a tandem repetition of the sequence TTAGGG. In normal cells, the DNA replication machinery is unable to completely duplicate the telomeric DNA; thus, telomeres are shortened after every cell division. Having reached a critical length, telomeres may be recognized as double strand break DNA lesions, and cells eventually enter senescence. Carcinogenesis is a multistep process involving multiple mutations and chromosomal aberrations. One of the most prevalent aberrations in pre-cancerous lesions is telomere shortening and telomerase activation. We discuss the role and homeostasis of telomeres in normal cells and their implication in the early steps of carcinogenesis. We also discuss various techniques used, and their limitations, in the study of telomeres and genome instability and their role in carcinogenesis and related genomic modifications.
authors.affiliation: Laboratory of Radiobiology and Oncology, DSV/IRCM/SRO/LRO, CEA, Fontenay-aux-Roses, France.
authors.forename: Christophe Michel
authors.initials: CM
authors.lastname: Raynaud
authors.forename: Laure
authors.initials: L
authors.lastname: Sabatier
authors.forename: Ophelie
authors.initials: O
authors.lastname: Philipot
authors.forename: Ken André
authors.initials: KA
authors.lastname: Olaussen
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Soria
mesh_terms: D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000378:metabolism; D004260:DNA Repair; D015972:Gene Expression Regulation, Neoplastic; D042822:Genomic Instability; D023281:Genomics / Q000379:methods; D006570:Heterochromatin / Q000378:metabolism; D006801:Humans; D009369:Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism; D000089804:Shelterin Complex; D019098:Telomerase / Q000378:metabolism; D016615:Telomere / Q000378:metabolism*; D034501:Telomere-Binding Proteins / Q000378:metabolism*
chemical_list: D006570:Heterochromatin; D000089804:Shelterin Complex; D034501:Telomere-Binding Proteins; D019098:Telomerase