0000000000331645
AUTHOR
Lara Pérez-martínez
Npl3 stabilizes R-loops at telomeres to prevent accelerated replicative senescence.
Abstract Telomere shortening rates must be regulated to prevent premature replicative senescence. TERRA R‐loops become stabilized at critically short telomeres to promote their elongation through homology‐directed repair (HDR), thereby counteracting senescence onset. Using a non‐bias proteomic approach to detect telomere binding factors, we identified Npl3, an RNA‐binding protein previously implicated in multiple RNA biogenesis processes. Using chromatin immunoprecipitation and RNA immunoprecipitation, we demonstrate that Npl3 interacts with TERRA and telomeres. Furthermore, we show that Npl3 associates with telomeres in an R‐loop‐dependent manner, as changes in R‐loop levels, for example, …
Chromatin modifiers and recombination factors promote a telomere fold-back structure, that is lost during replicative senescence.
Telomeres have the ability to adopt a lariat conformation and hence, engage in long and short distance intra-chromosome interactions. Budding yeast telomeres were proposed to fold back into subtelomeric regions, but a robust assay to quantitatively characterize this structure has been lacking. Therefore, it is not well understood how the interactions between telomeres and non-telomeric regions are established and regulated. We employ a telomere chromosome conformation capture (Telo-3C) approach to directly analyze telomere folding and its maintenance in S. cerevisiae. We identify the histone modifiers Sir2, Sin3 and Set2 as critical regulators for telomere folding, which suggests that a dis…