PXD035661 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Regulation of Rad52-dependent replication fork recovery through serine ADP-ribosylation of PolD3 |
Description | Although Poly(ADP-ribose)-polymerases (PARPs) are key regulators of genome stability, how site-specific ADP-ribosylation regulates DNA repair is unclear. Here, we describe a novel role for PARP1 and PARP2 in regulating Rad52-dependent replication fork repair to maintain cell viability when HR is dysfunctional, suppress replication-associated DNA damage, and maintain genome stability. Mechanistically, Mre11 is required for induction of PARP activity in response to replication stress that in turn promotes break-induced replication (BIR) through assembly of Rad52 at stalled/damaged replication forks. Further, by mapping ADP-ribosylation sites induced upon replication stress, we identify that PolD3 is a target for PARP1/PARP2 and importantly, that its site-specific ADP-ribosylation is required for BIR activity, replication fork recovery and genome stability. Overall, these data identify a critical role for Mre11-dependent PARP activation and site-specific ADP-ribosylation in regulating BIR to maintain genome integrity during DNA synthesis. |
HostingRepository | PRIDE |
AnnounceDate | 2023-10-24 |
AnnouncementXML | Submission_2023-10-24_11:13:24.485.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | SaraLarsen |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | adenosine diphosphoribosyl (ADP-ribosyl) modified residue |
Instrument | Orbitrap Fusion Lumos |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2022-08-01 02:04:41 | ID requested | |
⏵ 1 | 2023-10-24 11:13:25 | announced | |
2 | 2023-11-14 09:07:19 | announced | 2023-11-14: Updated project metadata. |
Publication List
Richards F, Llorca-Cardenosa MJ, Langton J, Buch-Larsen SC, Shamkhi NF, Sharma AB, Nielsen ML, Lakin ND, Regulation of Rad52-dependent replication fork recovery through serine ADP-ribosylation of PolD3. Nat Commun, 14(1):4310(2023) [pubmed] |
Keyword List
submitter keyword: proteomics, DNA repair, ADPr, PARPs, Lumos,ADP-ribosyltransferases, ADP-ribosylation, Af1521, DNA replication |
Contact List
Michael LundNielsen |
contact affiliation | Proteomics Program, Novo Nordisk Foundation Center for Protein Research, University of Copenhagen |
contact email | michael.lund.nielsen@cpr.ku.dk |
lab head | |
SaraLarsen |
contact affiliation | NNF Center for Protein Research |
contact email | sara.larsen@cpr.ku.dk |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD035661
- Label: PRIDE project
- Name: Regulation of Rad52-dependent replication fork recovery through serine ADP-ribosylation of PolD3