Retrotransposon-derived P53 Binding Sites Enhance Telomere Maintenance and Genome Protection

Overview

Journal Bioessays

Publisher Wiley

Specialties Biology
Cell Biology
Molecular Biology

Date 2016 Aug 20

PMID 27539745

Citations 3

Authors

Paul M Lieberman

Affiliations

Soon will be listed here.

Abstract

Tumor suppressor protein 53 (p53) plays a central role in the control of genome stability, acting primarily through the transcriptional activation of stress-response genes. However, many p53 binding sites are located at genomic locations with no obvious regulatory-link to known stress-response genes. We recently discovered p53 binding sites within retrotransposon-derived elements in human and mouse subtelomeres. These retrotransposon-derived p53 binding sites protected chromosome ends through transcription activation of telomere repeat RNA, as well as through the direct modification of local chromatin structure in response to DNA damage. Based on these findings, I hypothesize that a class of p53 binding sites, including the retrotransposon-derived p53-sites found in subtlomeres, provide a primary function in genome stability by mounting a direct and local protective chromatin-response to DNA damage. I speculate that retrotransposon-derived p53 binding sites share features with telomere-repeats through an evolutionary drive to monitor and maintain genome integrity.

Citing Articles

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The Rich World of p53 DNA Binding Targets: The Role of DNA Structure.

Brazda V, Fojta M Int J Mol Sci. 2019; 20(22).

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Germline TP53 mutations result into a constitutive defect of p53 DNA binding and transcriptional response to DNA damage.

Zerdoumi Y, Lanos R, Raad S, Flaman J, Bougeard G, Frebourg T Hum Mol Genet. 2017; 26(14):2591-2602.

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