Maintenance of a minimal telomere length is essential to prevent cellular senescence. When critically short telomeres arise in the absence of telomerase, they can be repaired by homology-directed repair (HDR) to prevent premature senescence onset. It is unclear why specifically the shortest telomeres are targeted for HDR. We demonstrate that the non-coding RNA TERRA accumulates as HDR-promoting RNA-DNA hybrids (R-loops) preferentially at very short telomeres. The increased level of TERRA and R-loops, exclusively at short telomeres, is due to a local defect in RNA degradation by the Rat1 and RNase H2 nucleases, respectively. Consequently, the coordination of TERRA degradation with telomere replication is altered at shortened telomeres. R-loop persistence at short telomeres contributes to activation of the DNA damage response (DDR) and promotes recruitment of the Rad51 recombinase. Thus, the telomere length-dependent regulation of TERRA and TERRA R-loops is a critical determinant of the rate of replicative senescence
Graf, M., Bonetti, D., Lockhart, A., Serhal, K., Kellner, V., Maicher, A., et al. (2017). Telomere Length Determines TERRA and R-Loop Regulation through the Cell Cycle. CELL, 170(1), 72-85.e14 [10.1016/j.cell.2017.06.006].
Citazione: | Graf, M., Bonetti, D., Lockhart, A., Serhal, K., Kellner, V., Maicher, A., et al. (2017). Telomere Length Determines TERRA and R-Loop Regulation through the Cell Cycle. CELL, 170(1), 72-85.e14 [10.1016/j.cell.2017.06.006]. | |
Tipo: | Articolo in rivista - Articolo scientifico | |
Carattere della pubblicazione: | Scientifica | |
Presenza di un coautore afferente ad Istituzioni straniere: | Si | |
Titolo: | Telomere Length Determines TERRA and R-Loop Regulation through the Cell Cycle | |
Autori: | Graf, M; Bonetti, D; Lockhart, A; Serhal, K; Kellner, V; Maicher, A; Jolivet, P; Teixeira, M; Luke, B | |
Autori: | BONETTI, DIEGO (Co-primo) | |
Data di pubblicazione: | 2017 | |
Lingua: | English | |
Rivista: | CELL | |
Digital Object Identifier (DOI): | http://dx.doi.org/10.1016/j.cell.2017.06.006 | |
Appare nelle tipologie: | 01 - Articolo su rivista |
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