Subtelomeric p53 binding prevents accumulation of DNA damage at human telomeres

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 H2AX 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.

Source: EMBO Journal - January 17, 2016 Category: Molecular Biology Authors: Tutton, S., Azzam, G. A., Stong, N., Vladimirova, O., Wiedmer, A., Monteith, J. A., Beishline, K., Wang, Z., Deng, Z., Riethman, H., McMahon, S. B., Murphy, M., Lieberman, P. M. Tags: DNA Replication, Repair & Recombination Articles Source Type: research