Acetyltransferase p300 regulates NBS1-mediated DNA damage response

被引：19
作者：
Jang, Eun Ryoung [1 ]
Choi, Jae Duk [1 ,2 ]
Lee, Jong-Soo [1 ]
机构：
[1] Ajou Univ, Coll Nat Sci, Dept Mol Sci & Technol, Suwon 443749, South Korea
[2] Seoul Natl Univ, Sch Biol Sci, Seoul 151, South Korea
来源：
FEBS LETTERS | 2011年 / 585卷 / 01期
基金：
新加坡国家研究基金会;
关键词：
p300; NBS1; Phosphorylation; Acetylation; ATM; DNA damage response; ATM; PROTEIN; TRANSCRIPTION; COMPLEX; PHOSPHORYLATION; COACTIVATOR; ACTIVATION; STABILITY; CBP/P300; CANCER;
D O I：
10.1016/j.febslet.2010.11.034
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
The role of p300 in DNA damage response is unclear. To understand how ATM-dependent phosphorylation of p300 affects its function in response to DNA damage, we present evidence that S106 of p300, which is phosphorylated by ATM, regulates stability of NBS1 and recruitment into damaged DNA, possibly leading to regulation of DNA repair. Non-phosphorylatable p300 (S106A) destabilized NBS1 and decreased NBS1-p300 interaction. The recruitment of NBS1 into damaged DNA was impaired in the presence of S106A. Also, a dominant negative p300 lacking enzymatic activity induced destabilization of NBS1, suggesting that its acetyltransferase is required for NBS1 stability. These results indicate that phosphorylation of p300 can regulate NBS1-mediated DNA damage response, and that these events occur in an acetylation-dependent manner. Structured summary: MINT-8058074, MINT-8058083:p300 (uniprotkb:Q09472) physically interacts (MI:0915) with NBS1 (uniprotkb:O60934) by anti bait coimmunoprecipitation (MI:0006) MINT-8058111:p300 (uniprotkb:Q09472) and NBS1 (uniprotkb:O60934) colocalize (MI:0403) by fluorescence microscopy (MI:0416) MINT-8058657:p300 (uniprotkb:Q09472) physically interacts (MI:0915) with NBS1 (uniprotkb:O60934) by two hybrid (MI:0018) MINT-8058093:p300 (uniprotkb:Q09472) physically interacts (MI:0915) with NBS1 (uniprotkb:O60934) by anti tag coimmunoprecipitation (MI:0007) (C) 2010 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.
引用
收藏
页码：47 / 52
页数：6
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