Lieberman Paul M
The Wistar Institute, Philadelphia, PA, USA.
Bioessays. 2016 Oct;38(10):943-9. doi: 10.1002/bies.201600078. Epub 2016 Aug 19.
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.
肿瘤抑制蛋白53（p53）在基因组稳定性控制中起核心作用，主要通过应激反应基因的转录激活发挥作用。然而，许多p53结合位点位于基因组位置，与已知的应激反应基因没有明显的调控联系。我们最近在人和小鼠亚端粒的逆转录转座子衍生元件中发现了p53结合位点。这些逆转录转座子衍生的p53结合位点通过端粒重复RNA的转录激活以及响应DNA损伤对局部染色质结构的直接修饰来保护染色体末端。基于这些发现，我推测一类p53结合位点，包括在亚端粒中发现的逆转录转座子衍生的p53位点，通过对DNA损伤产生直接和局部的保护性染色质反应，在基因组稳定性中发挥主要作用。我推测逆转录转座子衍生的p53结合位点通过监测和维持基因组完整性的进化驱动力与端粒重复序列具有共同特征。
