The THO complex component Thp2 counteracts telomeric R-loops and telomere shortening.
EMBO J
; 32(21): 2861-71, 2013 Oct 30.
Article
em En
| MEDLINE
| ID: mdl-24084588
ABSTRACT
Telomere maintenance by the conventional DNA replication machinery and telomerase is assisted by specialized DNA helicases, nucleases and telomere binding proteins. Here, we identify the THO components at telomeres and define critical roles of this complex in telomere stability. Deletion of the THO-subunit THP2 leads to telomere shortening. We discover that telomeres contain RNADNA hybrid structures or R-loops which involve the long-noncoding RNA TERRA and which accumulate in thp2-Δ cells. Telomere length is not restored by R-loop removal upon RNase H overexpression, but by deletion of Exonuclease 1 (Exo1). Replication stress further enhances the short telomere phenotype of THP2 mutants. Similar events occur upon induced transcription of TERRA and genetic analysis links Thp2 to TERRA function. Altogether, our data indicate that THO, through the interplay with TERRA, regulates chromosome end processing activities and prevents interference with semiconservative DNA replication of telomeric DNA.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Telômero
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Proteínas de Saccharomyces cerevisiae
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Proteínas de Ligação a DNA
Tipo de estudo:
Prognostic_studies
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article