Telomere Science Library

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Subtelomeric p53 binding prevents accumulation of DNA damage at human telomeres.

Authors: Stephen S. Tutton, Greggory A GA. Azzam, Nicholas N. Stong, Olga O. Vladimirova, Andreas A. Wiedmer, Jessica A JA. Monteith, Kate K. Beishline, Zhuo Z. Wang, Zhong Z. Deng, Harold H. Riethman, Steven B SB. McMahon, Maureen M. Murphy, Paul M PM. Lieberman
Published: 12/12/2015, The EMBO journal


Telomeres and tumor suppressor protein TP53 (p53) function in genome protection, but a direct role of p53 at telomeres has not yet been described. Here, we have identified non-canonical p53-binding sites within the human subtelomeres that suppress the accumulation of DNA damage at telomeric repeat DNA. These non-canonical subtelomeric p53-binding sites conferred transcription enhancer-like functions that include an increase in local histone H3K9 and H3K27 acetylation and stimulation of subtelomeric transcripts, including telomere repeat-containing RNA (TERRA). p53 suppressed formation of telomere-associated γH2AX and prevented telomere DNA degradation in response to DNA damage stress. Our findings indicate that p53 provides a direct chromatin-associated protection to human telomeres, as well as other fragile genomic sites. We propose that p53-associated chromatin modifications enhance local DNA repair or protection to provide a previously unrecognized tumor suppressor function of p53.

© 2015 The Authors.
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