Spontaneous telomere to telomere fusions occur in unperturbed fission yeast cells

Almeida, H.; Godinho Ferreira, M.

Publication

Spontaneous telomere to telomere fusions occur in unperturbed fission yeast cells

2013-03-01Journal article

dc.contributor.author	Almeida, H.
dc.contributor.author	Godinho Ferreira, M.
dc.date.accessioned	2015-10-21T13:52:28Z
dc.date.available	2015-10-21T13:52:28Z
dc.date.issued	2013-03-01
dc.description.abstract	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.	pt_PT
dc.description.sponsorship	FCT fellowship: (SFRH/BD/62050/2009), Association for International Cancer Research (Ref:06-396),	pt_PT
dc.identifier	10.1093/nar/gks1459
dc.identifier.citation	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	pt_PT
dc.identifier.doi	10.1093/nar/gks1459
dc.identifier.uri	http://hdl.handle.net/10400.7/422
dc.language.iso	eng	pt_PT
dc.peerreviewed	yes	pt_PT
dc.publisher	Oxford University Press	pt_PT
dc.relation	Inhibiton of genomic instability by telomere protection
dc.relation.publisherversion	http://nar.oxfordjournals.org/content/41/5/3056.long	pt_PT
dc.rights.uri	http://creativecommons.org/licenses/by-nc/4.0/	pt_PT
dc.subject	Telomere	pt_PT
dc.subject	Cells	pt_PT
dc.title	Spontaneous telomere to telomere fusions occur in unperturbed fission yeast cells	pt_PT
dc.type	journal article
dspace.entity.type	Publication
oaire.awardTitle	Inhibiton of genomic instability by telomere protection
oaire.awardURI	info:eu-repo/grantAgreement/FCT/3599-PPCDT/PTDC%2FSAU-OBD%2F66438%2F2006/PT
oaire.citation.endPage	3067	pt_PT
oaire.citation.issue	5	pt_PT
oaire.citation.startPage	3056	pt_PT
oaire.citation.title	Nucleic Acids Research	pt_PT
oaire.citation.volume	41	pt_PT
oaire.fundingStream	3599-PPCDT
project.funder.identifier	http://doi.org/10.13039/501100001871
project.funder.name	Fundação para a Ciência e a Tecnologia
rcaap.rights	openAccess	pt_PT
rcaap.type	article	pt_PT
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