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Human RAP 1 specifically protects telomeres of senescent cells from DNA damage
Author(s) -
Lototska Liudmyla,
Yue JiaXing,
Li Jing,
GiraudPanis MarieJosèphe,
Songyang Zhou,
Royle Nicola J,
Liti Gianni,
Ye Jing,
Gilson Eric,
MendezBermudez Aaron
Publication year - 2020
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.201949076
Subject(s) - telomere , telomerase , telomere binding protein , rap1 , microbiology and biotechnology , biology , activator (genetics) , dna , chemistry , genetics , dna binding protein , gene , transcription factor , signal transduction
Repressor/activator protein 1 ( RAP 1) is a highly evolutionarily conserved protein found at telomeres. Although yeast Rap1 is a key telomere capping protein preventing non‐homologous end joining ( NHEJ ) and consequently telomere fusions, its role at mammalian telomeres in vivo is still controversial. Here, we demonstrate that RAP 1 is required to protect telomeres in replicative senescent human cells. Downregulation of RAP 1 in these cells, but not in young or dividing pre‐senescent cells, leads to telomere uncapping and fusions. The anti‐fusion effect of RAP 1 was further explored in a HeLa cell line where RAP 1 expression was depleted through an inducible CRISPR /Cas9 strategy. Depletion of RAP 1 in these cells gives rise to telomere fusions only when telomerase is inhibited. We further show that the fusions triggered by RAP 1 loss are dependent upon DNA ligase IV . We conclude that human RAP 1 is specifically involved in protecting critically short telomeres. This has important implications for the functions of telomeres in senescent cells.