Please use this identifier to cite or link to this item: https://doi.org/10.1038/s41467-017-01805-9
Title: DNA damage causes rapid accumulation of phosphoinositides for ATR signaling
Authors: Wang, Y.-H 
Hariharan, A 
Bastianello, G
Toyama, Y 
Shivashankar, G.V 
Foiani, M
Sheetz, M.P 
Keywords: actin
ATR protein
cell nucleus receptor
checkpoint kinase 1
inositol polyphosphate
inositol polyphosphate multikinase
latrunculin A
messenger RNA
nuclear protein
nuclear receptor protein SF1
phosphatidylinositide
unclassified drug
wortmannin
ATM protein
ATR protein, human
checkpoint kinase 1
CHEK1 protein, human
inositol polyphosphate multikinase
phosphatidylinositol
phosphotransferase
steroidogenic factor 1
chemical reaction
DNA
enzyme
enzyme activity
metabolism
nervous system disorder
protein
animal cell
Article
controlled study
DNA damage response
DNA repair
embryo
enzyme activation
enzyme phosphorylation
gene expression
lipid storage
mouse
nonhuman
phosphoinositide metabolism
pleckstrin homology domain
protein assembly
protein binding
protein depletion
protein expression
RNA splicing
signal transduction
animal
cell line
DNA damage
genetics
human
metabolism
RNA interference
signal transduction
tumor cell line
Animals
Ataxia Telangiectasia Mutated Proteins
Cell Line
Cell Line, Tumor
Checkpoint Kinase 1
DNA Damage
DNA Repair
Humans
Mice
Phosphatidylinositols
Phosphotransferases (Alcohol Group Acceptor)
RNA Interference
Signal Transduction
Steroidogenic Factor 1
Issue Date: 2017
Publisher: Nature Publishing Group
Citation: Wang, Y.-H, Hariharan, A, Bastianello, G, Toyama, Y, Shivashankar, G.V, Foiani, M, Sheetz, M.P (2017). DNA damage causes rapid accumulation of phosphoinositides for ATR signaling. Nature Communications 8 (1) : 2118. ScholarBank@NUS Repository. https://doi.org/10.1038/s41467-017-01805-9
Abstract: 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. © 2017 The Author(s).
Source Title: Nature Communications
URI: https://scholarbank.nus.edu.sg/handle/10635/174372
ISSN: 2041-1723
DOI: 10.1038/s41467-017-01805-9
Appears in Collections:Elements
Staff Publications

Show full item record
Files in This Item:
File Description SizeFormatAccess SettingsVersion 
10_1038_s41467-017-01805-9.pdf4.24 MBAdobe PDF

OPEN

NoneView/Download

SCOPUSTM   
Citations

26
checked on Oct 22, 2020

Page view(s)

10
checked on Oct 22, 2020

Google ScholarTM

Check

Altmetric


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.