PXD035661

PXD035661 is an original dataset announced via ProteomeXchange.

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	2023-11-14
AnnouncementXML	Submission_2023-11-14_09:07:16.445.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Sara Larsen
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	adenosine diphosphoribosyl (ADP-ribosyl) modified residue
Instrument	Orbitrap Fusion Lumos

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.

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]

submitter keyword: proteomics, DNA repair, ADPr, PARPs, Lumos,ADP-ribosyltransferases, ADP-ribosylation, Af1521, DNA replication

Michael Lund Nielsen
contact affiliation	Proteomics Program, Novo Nordisk Foundation Center for Protein Research, University of Copenhagen
contact email	michael.lund.nielsen@cpr.ku.dk
lab head
Sara Larsen
contact affiliation	NNF Center for Protein Research
contact email	sara.larsen@cpr.ku.dk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD035661
     1. Label: PRIDE project
     2. Name: Regulation of Rad52-dependent replication fork recovery through serine ADP-ribosylation of PolD3