Drosophila UTX Coordinates with p53 to Regulate ku80 Expression in Response to DNA Damage

Chengwan Zhang,Zehui Hong,Da Ma,Wei Xie,Ming Fang,Yuchen Qian,Feng Tie,Wencui Ma,Rolf Müller

doi:10.1371/journal.pone.0078652

Chengwan Zhang, Zehui Hong + Show 7 more

Open Access

https://doi.org/10.1371/journal.pone.0078652

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Journal: PloS one	Publication Date: Nov 12, 2013
Citations: 61	License type: CC BY 4.0

Affiliation: Southeast University, Case Western Reserve University

Abstract

UTX is known as a general factor that activates gene transcription during development. Here, we demonstrate an additional essential role of UTX in the DNA damage response, in which it upregulates the expression of ku80 in Drosophila, both in cultured cells and in third instar larvae. We further showed that UTX mediates the expression of ku80 by the demethylation of H3K27me3 at the ku80 promoter upon exposure to ionizing radiation (IR) in a p53-dependent manner. UTX interacts physically with p53, and both UTX and p53 are recruited to the ku80 promoter following IR exposure in an interdependent manner. In contrast, the loss of utx has little impact on the expression of ku70, mre11, hid and reaper, suggesting the specific regulation of ku80 expression by UTX. Thus, our findings further elucidate the molecular function of UTX.

Highlights

Maintaining genomic stability is crucial for ensuring the accurate cellular functioning of organisms ranging from bacteria to humans [1,2]
To understand the mechanism underlying UTX function in tumorgenesis, we explored whether UTX is involved in DNA damage response in Drosophila
We found that UTX, play an essential role in DNA damage response by upregulation of ku80, which is uniquely required for p53 activated ku80 expression (Fig. 2–5)

Summary

Introduction

Maintaining genomic stability is crucial for ensuring the accurate cellular functioning of organisms ranging from bacteria to humans [1,2]. During the course of evolution, cells have evolved multiple mechanisms, collectively known as the DNA damage response (DDR), that facilitate the cellular response to DNA damage [3,4,5]. These mechanisms include cell-cycle arrest, DNA repair and apoptosis [6,7]. Over the last few years, a wealth of new information has been uncovered about the DDR, including the identification of many novel proteins involved in this process [12], but whether these proteins are regulated at the gene transcription level in response to DNA damage remains poorly understood

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