PXD045320

PXD045320 is an original dataset announced via ProteomeXchange.

Dataset Summary

Title	PARG is Essential for Pol-theta-Mediated DNA End-Joining by Removing Repressive Poly-ADP Ribose Marks
Description	DNA 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.
HostingRepository	MassIVE
AnnounceDate	2024-09-23
AnnouncementXML	Submission_2024-09-23_15:47:33.271.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Hsin-Yao Tang
SpeciesList	scientific name: Homo sapiens; common name: human; NCBI TaxID: 9606;
ModificationList	Deamidated; Oxidation
Instrument	Q Exactive Plus

Dataset History

Revision	Datetime	Status	ChangeLog Entry
0	2023-09-12 12:37:23	ID requested
⏵ 1	2024-09-23 15:47:34	announced

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]

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

submitter keyword: DNA polymerase theta, PARP1

Contact List

Tomasz Skorski
contact affiliation	Temple University
contact email	tomasz.skorski@temple.edu
lab head
Hsin-Yao Tang
contact affiliation	The Wistar Institute
contact email	tangh@wistar.org
dataset submitter

Full Dataset Link List

MassIVE dataset URI
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MassIVE dataset URI

Dataset FTP location
NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://massive.ucsd.edu/v06/MSV000092839/