title: Life and cancer without telomerase: ALT and other strategies for making sure ends (don't) meet.
abstract: While most cancer cells rely on telomerase expression/re-activation for linear chromosome maintenance and sustained proliferation, a significant population of cancers (10-15%) employs telomerase-independent strategies, collectively dubbed Alternative Lengthening of Telomeres (ALT). Most ALT cells relax the usual role of telomeres as inhibitors of local homologous recombination while maintaining the ability of telomeres to prohibit local non-homologous end joining reactions. Here we review current concepts surrounding how ALT telomeres achieve this new balance via alterations in chromatin landscape, DNA damage repair processes and handling of telomeric transcription. We also discuss telomerase independent end maintenance strategies utilized by other organisms, including fruitflies and yeasts, to draw parallels and contrasts and highlight additional modes, beyond ALT, that may be available to telomerase-minus cancers. We conclude by commenting on promises and challenges in the development of effective anti-ALT cancer therapies.
authors.affiliation: a Laboratory of Biochemistry and Molecular Biology , Center for Cancer Research, National Cancer Institute, NIH , Bethesda , MD , USA.
authors.forename: Manasi S
authors.initials: MS
authors.lastname: Apte
authors.affiliation: a Laboratory of Biochemistry and Molecular Biology , Center for Cancer Research, National Cancer Institute, NIH , Bethesda , MD , USA.
authors.forename: Julia Promisel
authors.initials: JP
authors.lastname: Cooper
mesh_terms: D000818:Animals; D002843:Chromatin / Q000235:genetics / Q000378:metabolism; D004249:DNA Damage; D004260:DNA Repair; D019143:Evolution, Molecular; D042822:Genomic Instability; D006570:Heterochromatin / Q000235:genetics / Q000378:metabolism; D059765:Homologous Recombination; D006801:Humans; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism / Q000628:therapy; D019098:Telomerase / Q000235:genetics / Q000378:metabolism*; D016615:Telomere / Q000235:genetics / Q000378:metabolism*; D059505:Telomere Homeostasis; D014158:Transcription, Genetic
chemical_list: D002843:Chromatin; D006570:Heterochromatin; D019098:Telomerase
keywords: ALT; DNA damage response; HAATI; Telomere; chromatin; genome stability; heterochromatin; recombination; telomerase