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PXD045320

PXD045320 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitlePARG is Essential for Pol-theta-Mediated DNA End-Joining by Removing Repressive Poly-ADP Ribose Marks
DescriptionDNA polymerase theta (Pol-theta)-mediated end-joining (TMEJ) repairs DNA double-strand breaks and confers resistance to genotoxic agents. How Pol-theta is regulated at the molecular level to exert TMEJ remains unknown. We find that Pol-theta interacts with and is PARylated by PARP1 in vitro and in cells. PARP1 recruits Pol-theta to the vicinity of DNA damage via PARylation dependent liquid demixing, however, PARylated Pol-theta (PAR-Pol-theta) cannot perform TMEJ due to its inability to bind DNA. PARG-mediated de-PARylation of Pol-theta reactivates its DNA binding and end-joining activities in vitro. Consistent with this, PARG is essential for TMEJ in cells and the temporal recruitment of PARG to DNA damage corresponds with TMEJ activation and dissipation of PARP1 and PAR. These studies support a two-step spatiotemporal mechanism of TMEJ regulation. First, PARP1 PARylates Pol-theta and facilitates its recruitment to DNA damage sites in an inactivated state. PARG subsequently activates TMEJ by removing repressive PAR marks on Pol-theta.
HostingRepositoryMassIVE
AnnounceDate2024-09-23
AnnouncementXMLSubmission_2024-09-23_15:47:33.271.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterHsin-Yao Tang
SpeciesList scientific name: Homo sapiens; common name: human; NCBI TaxID: 9606;
ModificationListDeamidated; Oxidation
InstrumentQ Exactive Plus
Dataset History
RevisionDatetimeStatusChangeLog Entry
02023-09-12 12:37:23ID requested
12024-09-23 15:47:34announced
Publication List
Vekariya U, Minakhin L, Chandramouly G, Tyagi M, Kent T, Sullivan-Reed K, Atkins J, Ralph D, Nieborowska-Skorska M, Kukuyan AM, Tang HY, Pomerantz RT, Skorski T, -mediated DNA end-joining by removing repressive poly-ADP-ribose marks. Nat Commun, 15(1):5822(2024) [pubmed]
Keyword List
submitter keyword: DNA polymerase theta, PARP1
Contact List
Tomasz Skorski
contact affiliationTemple University
contact emailtomasz.skorski@temple.edu
lab head
Hsin-Yao Tang
contact affiliationThe Wistar Institute
contact emailtangh@wistar.org
dataset submitter
Full Dataset Link List
MassIVE dataset URI
Dataset FTP location
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