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|Título:||Spontaneous telomere to telomere fusions occur in unperturbed fission yeast cells|
Godinho Ferreira, M.
|Editora:||Oxford University Press|
|Citação:||Hugo Almeida and Miguel Godinho Ferreira Spontaneous telomere to telomere fusions occur in unperturbed fission yeast cells Nucl. Acids Res. (2013) 41 (5): 3056-3067 first published online January 18, 2013 doi:10.1093/nar/gks1459|
|Resumo:||Telomeres protect eukaryotic chromosomes from illegitimate end-to-end fusions. When this function fails, dicentric chromosomes are formed, triggering breakage-fusion-bridge cycles and genome instability. How efficient is this protection mechanism in normal cells is not fully understood. We created a positive selection assay aimed at capturing chromosome-end fusions in Schizosaccharomyces pombe. We placed telomere sequences with a head to head arrangement in an intron of a selectable marker contained on a plasmid. By linearizing the plasmid between the telomere sequences, we generated a stable mini-chromosome that fails to express the reporter gene. Whenever the ends of the mini-chromosome join, the marker gene is reconstituted and fusions are captured by direct selection. Using telomerase mutants, we recovered several fusion events that lacked telomere sequences. The end-joining reaction involved specific homologous subtelomeric sequences capable of forming hairpins, suggestive of ssDNA stabilization prior to fusing. These events occurred via microhomology-mediated end-joining (MMEJ)/single-strand annealing (SSA) repair and also required MRN/Ctp1. Strikingly, we were able to capture spontaneous telomere-to-telomere fusions in unperturbed cells. Similar to disruption of the telomere regulator Taz1/TRF2, end-joining reactions occurred via non-homologous end-joining (NHEJ) repair. Thus, telomeres undergo fusions prior to becoming critically short, possibly through transient deprotection. These dysfunction events induce chromosome instability and may underlie early tumourigenesis.|
|Versão do Editor:||http://nar.oxfordjournals.org/content/41/5/3056.long|
|Aparece nas colecções:||TGS - Artigos|
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|Nucl. Acids Res.-2013-Almeida-3056-67.pdf||artigo principal||5,5 MB||Adobe PDF||Ver/Abrir|
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