Subtelomeric p53 binding prevents accumulation of DNA damage at human telomeres

EMBO J. 2016 Jan 18;35(2):193-207. doi: 10.15252/embj.201490880. Epub 2015 Dec 12.


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.

Keywords: DNA damage; TERRA; TP53; chromatin; telomere; tumor suppressor.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • DNA Damage / genetics*
  • HCT116 Cells
  • Humans
  • Protein Binding
  • Telomere / genetics
  • Telomere / metabolism*
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism*


  • Carrier Proteins
  • Tumor Suppressor Protein p53