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] |
Keyword List
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 |
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/ |