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DOI | 10.1038/s41467-018-06973-w |
DNA damage causes rapid accumulation of phosphoinositides for ATR signaling | |
Wang, Yu-Hsiu1; Hariharan, Anushya1; Bastianello, Giulia2,3; Toyama, Yusuke1,4,5; Shivashankar, G. V.1,2,5; Foiani, Marco2,3; Sheetz, Michael P.1,6 | |
2017-12-14 | |
发表期刊 | NATURE COMMUNICATIONS |
ISSN | 2041-1723 |
出版年 | 2017 |
卷号 | 8 |
文章类型 | Article |
语种 | 英语 |
国家 | Singapore; Italy; USA |
英文摘要 | Phosphoinositide lipids (PPIs) are enriched in the nucleus and are accumulated at DNA damage sites. Here, we investigate roles of nuclear PPIs in DNA damage response by sequestering specific PPIs with the expression of nuclear-targeted PH domains, which inhibits recruitment of Ataxia telangiectasia and Rad3-related protein (ATR) and reduces activation of Chk1. PPI-binding domains rapidly (< 1 s) accumulate at damage sites with local enrichment of PPIs. Accumulation of PIP3 in complex with the nuclear receptor protein, SF1, at damage sites requires phosphorylation by inositol polyphosphate multikinase (IPMK) and promotes nuclear actin assembly that is required for ATR recruitment. Suppressed ATR recruitment/activation is confirmed with latrunculin A and wortmannin treatment as well as IPMK or SF1 depletion. Other DNA repair pathways involving ATM and DNA-PKcs are unaffected by PPI sequestration. Together, these findings reveal that nuclear PPI metabolism mediates an early damage response through the IPMK-dependent pathway to specifically recruit ATR. |
领域 | 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000417906400002 |
WOS关键词 | INOSITOL POLYPHOSPHATE MULTIKINASE ; PLECKSTRIN HOMOLOGY DOMAINS ; LIVER NUCLEAR ENVELOPES ; BRUTONS TYROSINE KINASE ; MESSENGER-RNA EXPORT ; STRAND BREAK REPAIR ; PH DOMAIN ; PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE ; HUMAN GENOME ; PROTEINS |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
URL | 查看原文 |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/204070 |
专题 | 资源环境科学 |
作者单位 | 1.Natl Univ Singapore, Mechanobiol Inst, Singapore 117411, Singapore; 2.FIRC Inst Mol Oncol, IFOM, Via Adamello 16, I-20139 Milan, Italy; 3.Univ Milan, I-20133 Milan, Italy; 4.Temasek Life Sci Lab, 1 Res Link, Singapore 117604, Singapore; 5.Natl Univ Singapore, Dept Biol Sci, Singapore 117543, Singapore; 6.Columbia Univ, Dept Biol Sci, New York, NY 10027 USA |
推荐引用方式 GB/T 7714 | Wang, Yu-Hsiu,Hariharan, Anushya,Bastianello, Giulia,et al. DNA damage causes rapid accumulation of phosphoinositides for ATR signaling[J]. NATURE COMMUNICATIONS,2017,8. |
APA | Wang, Yu-Hsiu.,Hariharan, Anushya.,Bastianello, Giulia.,Toyama, Yusuke.,Shivashankar, G. V..,...&Sheetz, Michael P..(2017).DNA damage causes rapid accumulation of phosphoinositides for ATR signaling.NATURE COMMUNICATIONS,8. |
MLA | Wang, Yu-Hsiu,et al."DNA damage causes rapid accumulation of phosphoinositides for ATR signaling".NATURE COMMUNICATIONS 8(2017). |
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