PXD009650-1

PXD009650 is an original dataset announced via ProteomeXchange.

Title	53BP1 cooperation with the REV7–shieldin complex underpins DNA structure-specific NHEJ
Description	53BP1 governs a specialized, context-specific branch of the classical non-homologous end joining DNA double-strand break repair pathway. Mice lacking 53bp1 (also known as Trp53bp1) are immunodeficient owing to a complete loss of immunoglobulin class-switch recombination, and reduced fidelity of long-range V(D)J recombination. The 53BP1-dependent pathway is also responsible for pathological joining events at dysfunctional telomeres, and its unrestricted activity in Brca1-deficient cellular and tumour models causes genomic instability and oncogenesis. Cells that lack core non-homologous end joining proteins are profoundly radiosensitive, unlike 53BP1-deficient cells, which suggests that 53BP1 and its co-factors act on specific DNA substrates. Here we show that 53BP1 cooperates with its downstream effector protein REV7 to promote non-homologous end joining during class-switch recombination, but REV7 is not required for 53BP1-dependent V(D)J recombination. We identify shieldin—a four-subunit putative single-stranded DNA-binding complex comprising REV7, c20orf196 (SHLD1), FAM35A (SHLD2) and FLJ26957 (SHLD3)— as the factor that explains this specificity. Shieldin is essential for REV7-dependent DNA end-protection and non-homologous end joining during class-switch recombination, and supports toxic non-homologous end joining in Brca1-deficient cells, yet is dispensable for REV7-dependent interstrand cross-link repair. The 53BP1 pathway therefore comprises distinct double-strand break repair activities within chromatin and single-stranded DNA compartments, which explains both the immunological differences between 53bp1- and Rev7- deficient mice and the context specificity of the pathway.
HostingRepository	PRIDE
AnnounceDate	2018-07-26
AnnouncementXML	Submission_2018-07-26_08:17:54.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD009650
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Roman Fischer
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	Ethyl; Ammonia-loss; Cation:Fe[II]; Amidated; Methyl; Oxidation; Methylphosphonate; Ethanolyl; Carboxy; CAMthiopropanoyl; Decanoyl; Propionamide; Phospho; GlycerylPE; Cation:Zn[II]; Didehydro; Cation:Na; Deamidated; Trp->Kynurenin; Acetyl; GlyGly; Malonyl; Delta:S(-1)Se(1); Formyl; Carbamyl; Carbamidomethyl; Cation:Ca[II]; Gln->pyro-Glu; Guanidinyl; Dehydrated; Dioxidation; Hydroxymethyl; MercaptoEthanol
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2018-05-02 10:42:40	ID requested
⏵ 1	2018-07-26 08:17:54	announced
2	2018-07-26 08:25:28	announced	Updated publication reference for DOI(s): 10.1038/s41586-018-0362-1s41586-018-0362-1.
3	2018-07-27 08:40:09	announced	Updated publication reference for DOI(s): 10.1038/s41586-018-0362-1s41586-018-0362-1.
4	2024-10-22 04:44:58	announced	2024-10-22: Updated project metadata.

s41586-018-0362-1;

curator keyword: Biological

submitter keyword: REV7 Shieldin

Roman Fischer
contact affiliation	Target Discovery Institute, University of Oxford
contact email	roman.fischer@ndm.ox.ac.uk
lab head
Roman Fischer
contact affiliation	University of Oxford
contact email	roman.fischer@ndm.ox.ac.uk
dataset submitter

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://ftp.pride.ebi.ac.uk/pride/data/archive/2018/07/PXD009650

PRIDE project URI

• PRIDE
  1. PXD009650
     1. Label: PRIDE project
     2. Name: 53BP1 cooperation with the REV7–shieldin complex underpins DNA structure-specific NHEJ