Please use this identifier to cite or link to this item: https://doi.org/10.1038/s41467-017-01805-9
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dc.titleDNA damage causes rapid accumulation of phosphoinositides for ATR signaling
dc.contributor.authorWang, Y.-H
dc.contributor.authorHariharan, A
dc.contributor.authorBastianello, G
dc.contributor.authorToyama, Y
dc.contributor.authorShivashankar, G.V
dc.contributor.authorFoiani, M
dc.contributor.authorSheetz, M.P
dc.date.accessioned2020-09-04T02:26:35Z
dc.date.available2020-09-04T02:26:35Z
dc.date.issued2017
dc.identifier.citationWang, 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
dc.identifier.issn2041-1723
dc.identifier.urihttps://scholarbank.nus.edu.sg/handle/10635/174372
dc.description.abstractPhosphoinositide 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).
dc.publisherNature Publishing Group
dc.sourceUnpaywall 20200831
dc.subjectactin
dc.subjectATR protein
dc.subjectcell nucleus receptor
dc.subjectcheckpoint kinase 1
dc.subjectinositol polyphosphate
dc.subjectinositol polyphosphate multikinase
dc.subjectlatrunculin A
dc.subjectmessenger RNA
dc.subjectnuclear protein
dc.subjectnuclear receptor protein SF1
dc.subjectphosphatidylinositide
dc.subjectunclassified drug
dc.subjectwortmannin
dc.subjectATM protein
dc.subjectATR protein, human
dc.subjectcheckpoint kinase 1
dc.subjectCHEK1 protein, human
dc.subjectinositol polyphosphate multikinase
dc.subjectphosphatidylinositol
dc.subjectphosphotransferase
dc.subjectsteroidogenic factor 1
dc.subjectchemical reaction
dc.subjectDNA
dc.subjectenzyme
dc.subjectenzyme activity
dc.subjectmetabolism
dc.subjectnervous system disorder
dc.subjectprotein
dc.subjectanimal cell
dc.subjectArticle
dc.subjectcontrolled study
dc.subjectDNA damage response
dc.subjectDNA repair
dc.subjectembryo
dc.subjectenzyme activation
dc.subjectenzyme phosphorylation
dc.subjectgene expression
dc.subjectlipid storage
dc.subjectmouse
dc.subjectnonhuman
dc.subjectphosphoinositide metabolism
dc.subjectpleckstrin homology domain
dc.subjectprotein assembly
dc.subjectprotein binding
dc.subjectprotein depletion
dc.subjectprotein expression
dc.subjectRNA splicing
dc.subjectsignal transduction
dc.subjectanimal
dc.subjectcell line
dc.subjectDNA damage
dc.subjectgenetics
dc.subjecthuman
dc.subjectmetabolism
dc.subjectRNA interference
dc.subjectsignal transduction
dc.subjecttumor cell line
dc.subjectAnimals
dc.subjectAtaxia Telangiectasia Mutated Proteins
dc.subjectCell Line
dc.subjectCell Line, Tumor
dc.subjectCheckpoint Kinase 1
dc.subjectDNA Damage
dc.subjectDNA Repair
dc.subjectHumans
dc.subjectMice
dc.subjectPhosphatidylinositols
dc.subjectPhosphotransferases (Alcohol Group Acceptor)
dc.subjectRNA Interference
dc.subjectSignal Transduction
dc.subjectSteroidogenic Factor 1
dc.typeArticle
dc.contributor.departmentMECHANOBIOLOGY INSTITUTE
dc.contributor.departmentDEPT OF BIOLOGICAL SCIENCES
dc.contributor.departmentBIOLOGY (NU)
dc.description.doi10.1038/s41467-017-01805-9
dc.description.sourcetitleNature Communications
dc.description.volume8
dc.description.issue1
dc.description.page2118
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