title: p300-mediated acetylation of TRF2 is required for maintaining functional telomeres.
abstract: The human telomeric protein TRF2 is required to protect chromosome ends by facilitating their organization into the protective capping structure. Post-translational modifications of TRF2 such as phosphorylation, ubiquitination, SUMOylation, methylation and poly(ADP-ribosyl)ation have been shown to play important roles in telomere function. Here we show that TRF2 specifically interacts with the histone acetyltransferase p300, and that p300 acetylates the lysine residue at position 293 of TRF2. We also report that p300-mediated acetylation stabilizes the TRF2 protein by inhibiting its ubiquitin-dependent proteolysis and is required for efficient telomere binding of TRF2. Furthermore, overexpression of the acetylation-deficient mutant, K293R, induces DNA-damage response foci at telomeres, thereby leading to induction of impaired cell growth, cellular senescence and altered cell cycle distribution. A small but significant number of metaphase chromosomes show no telomeric signals at chromatid ends, suggesting an aberrant telomere structure. These findings demonstrate that acetylation of TRF2 by p300 plays a crucial role in the maintenance of functional telomeres as well as in the regulation of the telomere-associated DNA-damage response, thus providing a new route for modulating telomere protection function.
authors: Departments of Systems Biology and Integrated Omics for Biomedical Science, WCU Program of Graduate School, Yonsei University, Seoul 120-749, Korea.
authors: Yoon Ra
authors: YR
authors: Her
authors: In Kwon
authors: IK
authors: Chung
mesh_terms: D000107:Acetylation; D019943:Amino Acid Substitution; D002460:Cell Line; D049109:Cell Proliferation; D004249:DNA Damage; D006801:Humans; D017434:Protein Structure, Tertiary; D059748:Proteolysis; D016615:Telomere / Q000378:metabolism*; D035341:Telomeric Repeat Binding Protein 2 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D025801:Ubiquitin / Q000378:metabolism; D050880:p300-CBP Transcription Factors / Q000378:metabolism*; D000099224:p300-CBP-Associated Factor
chemical_list: D035341:Telomeric Repeat Binding Protein 2; D025801:Ubiquitin; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor; C504753:TERF2 protein, human