PXD045534-1

PXD045534 is an original dataset announced via ProteomeXchange.

Title	Shieldin/CST-dependent and independent functions of 53BP1 control DNA end-joining and repair pathway choice
Description	53BP1 regulates DNA end-joining in lymphocytes, diversifying immune antigen receptors. This involves nucleosome-bound 53BP1 at DNA double-stranded breaks (DSBs) recruiting RIF1 and shieldin, a poorly understood DNA-binding complex. The 53BP1-RIF1-shieldin axis is pathological in BRCA1-mutated cancers, blocking homologous recombination (HR) and driving illegitimate non-homologous end-joining (NHEJ). However, how this axis regulates DNA end-joining and HR suppression remains unresolved. We investigated shieldin and its interplay with CST, a complex recently implicated in 53BP1-dependent activities. Immunophenotypically, mice lacking shieldin or CST are equivalent, with class-switch recombination co-reliant on both complexes. DNA damage-responsive signalling promotes shieldin-CST interaction, demonstrating shieldin as a DSB-specific CST adaptor. Furthermore, DNA polymerase ζ functions downstream of shieldin, establishing DNA fill-in synthesis as the physiological function of shieldin-CST. Lastly, 53BP1 suppresses HR and promotes NHEJ in BRCA1-deficient cells independently of shieldin. These findings showcase the resilience of the 53BP1 pathway, achieved through the collaboration of chromatin-bound 53BP1 complexes and DNA end-processing effector proteins.
HostingRepository	PRIDE
AnnounceDate	2024-08-27
AnnouncementXML	Submission_2024-08-27_14:23:48.822.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD045534
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Robert Parker
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	phosphorylated residue; acetylated residue; deamidated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2023-09-20 14:24:53	ID requested
⏵ 1	2024-08-27 14:23:49	announced
2	2024-10-22 06:56:47	announced	2024-10-22: Updated project metadata.

10.6019/PXD045534;

10.1038/S41594-024-01381-9;

submitter keyword: CST, Shieldin, DNA damage response

J. Ross Chapman
contact affiliation	Genome Integrity laboratory, Medical Research Council Molecular Haematology Unit, MRC Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, The University of Oxford, Oxford, UK
contact email	ross.chapman@imm.ox.ac.uk
lab head
Robert Parker
contact affiliation	Jenner Institute
contact email	robert.rparker@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD045534
     1. Label: PRIDE project
     2. Name: Shieldin/CST-dependent and independent functions of 53BP1 control DNA end-joining and repair pathway choice