PXD035345

PXD035345 is an original dataset announced via ProteomeXchange.

Title	BRCA1/BARD1 intrinsically disordered regions facilitate chromatin recruitment and ubiquitylation
Description	BRCA1/BARD1 is a tumor suppressor E3 ubiquitin (Ub) ligase with roles in DNA damage repair and in transcriptional regulation. BRCA1/BARD1 RING domains interact with nucleosomes to facilitate mono-ubiquitylation of distinct residues on the C-terminal tail of histone H2A. These enzymatic domains constitute a small fraction of the heterodimer, raising the possibility of functional chromatin interactions involving other regions such as the BARD1 C-terminal domains that bind nucleosomes containing the DNA damage signal H2A K15-Ub and H4 K20me0, or portions of the expansive intrinsically disordered regions found in both subunits. Herein, we reveal novel interactions that support robust H2A ubiquitylation activity mediated through a high-affinity, intrinsically disordered DNA-binding region of BARD1. These interactions support BRCA1/BARD1 recruitment to chromatin and sites of DNA damage in cells and contribute to their survival. We also reveal distinct BRCA1/BARD1 complexes that depend on the presence of H2A K15-Ub, including a complex where a single BARD1 subunit spans adjacent nucleosome units. Our findings identify an extensive network of multivalent BARD1-nucleosome interactions that serve as a platform for BRCA1/BARD1-associated functions on chromatin.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_09:01:23.261.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Alex Zelter
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2022-07-14 07:24:06	ID requested
1	2023-06-21 09:38:37	announced
⏵ 2	2023-11-14 09:01:27	announced	2023-11-14: Updated project metadata.

Witus SR, Tuttle LM, Li W, Zelter A, Wang M, Kermoade KE, Wilburn DB, Davis TN, Brzovic PS, Zhao W, Klevit RE, BRCA1/BARD1 intrinsically disordered regions facilitate chromatin recruitment and ubiquitylation. EMBO J, 42(15):e113565(2023) [pubmed]

submitter keyword: Kojak, BRCA1, cancer, nucleosome,Cross-linking Mass Spectrometry, ProXL, H2A, XL-MS, BARD1, tumor, ubiquitin ligase

Rachel E. Klevit
contact affiliation	Department of Biochemistry, University of Washington, Seattle, WA, USA
contact email	klevit@uw.edu
lab head
Alex Zelter
contact affiliation	Department of Biochemistry, University of Washington, Seattle
contact email	azelter@uw.edu
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/2023/06/PXD035345

PRIDE project URI

• PRIDE
  1. PXD035345
     1. Label: PRIDE project
     2. Name: BRCA1/BARD1 intrinsically disordered regions facilitate chromatin recruitment and ubiquitylation