Cancer cells activate telomere maintenance mechanisms (TMMs) to bypass replicative senescence and achieve immortality by either upregulating telomerase or promoting homology-directed repair (HDR) at chromosome ends to maintain telomere length, the latter being referred to as ALT (Alternative Lengthening of Telomeres). In yeast telomerase mutants, the HDR-based repair of telomeres leads to the generation of 'survivors’ that escape senescence and divide indefinitely. So far, yeast has proven to provide an accurate model to study the generation and maintenance of telomeres via HDR. Recently, it has been established that up-regulation of the lncRNA, TERRA (telomeric repeat-containing RNA), is a novel hallmark of ALT cells. Moreover, RNA-DNA hybrids are thought to trigger HDR at telomeres in ALT cells to maintain telomere length and function. Here we show that, also in established yeast type II survivors, TERRA levels are increased in an analogous manner to human ALT cells. The elevated TERRA levels are independent of yeast-specific subtelomeric structures, i.e. the presence or absence of Y’ repetitive elements. Furthermore, we show that RNase H1 overexpression, which degrades the RNA moiety in RNA-DNA hybrids, impairs the growth of yeast survivors. We suggest that even in terms of TERRA regulation, yeast survivors serve as an accurate model that recapitulates many key features of human ALT cells

Misino, S., Bonetti, D., Luke-Glaser, S., & Luke, B. (2018). Increased TERRA levels and RNase H sensitivity are conserved hallmarks of post-senescent survivors in budding yeast. DIFFERENTIATION, 100, 37-45 [10.1016/j.diff.2018.02.002].

Increased TERRA levels and RNase H sensitivity are conserved hallmarks of post-senescent survivors in budding yeast

Bonetti, D
Membro del Collaboration Group
;
2018

Abstract

Cancer cells activate telomere maintenance mechanisms (TMMs) to bypass replicative senescence and achieve immortality by either upregulating telomerase or promoting homology-directed repair (HDR) at chromosome ends to maintain telomere length, the latter being referred to as ALT (Alternative Lengthening of Telomeres). In yeast telomerase mutants, the HDR-based repair of telomeres leads to the generation of 'survivors’ that escape senescence and divide indefinitely. So far, yeast has proven to provide an accurate model to study the generation and maintenance of telomeres via HDR. Recently, it has been established that up-regulation of the lncRNA, TERRA (telomeric repeat-containing RNA), is a novel hallmark of ALT cells. Moreover, RNA-DNA hybrids are thought to trigger HDR at telomeres in ALT cells to maintain telomere length and function. Here we show that, also in established yeast type II survivors, TERRA levels are increased in an analogous manner to human ALT cells. The elevated TERRA levels are independent of yeast-specific subtelomeric structures, i.e. the presence or absence of Y’ repetitive elements. Furthermore, we show that RNase H1 overexpression, which degrades the RNA moiety in RNA-DNA hybrids, impairs the growth of yeast survivors. We suggest that even in terms of TERRA regulation, yeast survivors serve as an accurate model that recapitulates many key features of human ALT cells
Articolo in rivista - Articolo scientifico
Scientifica
Molecular Biology; Developmental Biology; Cell Biology; Cancer Research
English
Misino, S., Bonetti, D., Luke-Glaser, S., & Luke, B. (2018). Increased TERRA levels and RNase H sensitivity are conserved hallmarks of post-senescent survivors in budding yeast. DIFFERENTIATION, 100, 37-45 [10.1016/j.diff.2018.02.002].
Misino, S; Bonetti, D; Luke-Glaser, S; Luke, B
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/10281/189204
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