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Induction of a p95/Nbs1‐mediated S phase checkpoint by telomere 3′ overhang specific DNA
Author(s) -
Eller Mark S.,
Li GuangZhi,
Firoozabadi Reza,
Puri Neelu,
Gilchrest Barbara A.
Publication year - 2003
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.02-0197com
Subject(s) - telomere , dna damage , g2 m dna damage checkpoint , microbiology and biotechnology , cell cycle checkpoint , biology , dna repair , chek1 , cell cycle , telomere binding protein , nijmegen breakage syndrome , genome instability , dna , cancer research , genetics , apoptosis , dna binding protein , gene , transcription factor , ataxia telangiectasia
Telomere shortening induces a nonproliferative senescent phenotype, believed to reduce cancer risk, and telomeres are involved in a poorly understood manner in responses to DNA damage. Although telomere disruption induces p53 and triggers apoptosis or cell cycle arrest, the features of the disrupted telomere that trigger this response and the precise mechanism involved are poorly understood. Using human cells, we show that DNA oligonucleotides homologous to the telomere 3′ overhang sequence specifically induce and activate p53 and activate an S phase checkpoint by modifying the Nijmegen breakage syndrome protein, known to mediate the S phase checkpoint after DNA damage. These responses are mediated, at least in part, by the ATM kinase and are not attributable to disruption of cellular telomeres. Based on these and earlier data, we propose that these oligonucleotides mimic a physiological signal, exposure of the telomere 3′ overhang due to opening of the normal telomere loop structure, and hence evoke these protective anti‐proliferative responses in the absence of DNA damage or telomere disruption. Eller, M. S., Li, G.‐Z., Firoozabadi, R., Puri, N., Gilchrest, B. A. Induction of a P95/NBS1‐mediated S phase checkpoint by telomere 3′ overhang specific DNA. FASEB J . 17, 152–162 (2003)