PXD016700

PXD016700 is an original dataset announced via ProteomeXchange.

Title	Affinity Purification experiments for 24 human Bromodomain proteins involved in DNA repair and genome integrity (part 1 of 2).
Description	Bromodomain proteins (BRD) are key chromatin regulators of genome function and stability, as well as therapeutic targets in cancer. In our associated publication (doi:10.1101/gad.331231.119) we systematically delineate the contribution of human BRD proteins for genome stability and DNA double-strand break (DSB) repair using cell-based assays and proteomic interaction network analysis. These AP-MS experiments were performed in order to construct a protein interaction network for the 24 BRDs we identified as promoters of DNA repair and/or genome integrity: BAZ1B, BRD1, BRD2, BRD3, BRD4, BRD8, BRD9, BRPF3, BRWD3, CECR2, EP300, GCN5/KAT2A, PCAF/KAT2B, PHIP, SMARCA2, SP100, SP110, SP140, TAF1, TRIM24, TRIM28, TRIM33, TRIM66, ZMYND8. In combination with cell based assays, we identified a BRD-reader function of PCAF that bound TIP60-mediated histone acetylations at DSBs to recruit a DUB complex to deubiquitylate histone H2BK120, to allow direct acetylation by PCAF and repair of DSBs by homologous recombination. We also discovered the bromo-and-extra-terminal (BET) BRD proteins, BRD2 and BRD4, as negative regulators of transcription-associated RNA-DNA hybrid (R-Loop) as inhibition of BRD2 or BRD4 increased R-loop formation, which generated DSBs. These breaks were reliant on Topoisomerase II and BRD2 directly bound and activated Topoisomerase I, a known restrainer of R-loops. Thus, comprehensive interactome and functional profiling of BRD proteins revealed new homologous recombination and genome stability pathways, providing a strategy to understand genome maintenance by BRD proteins and the effects of their pharmacological inhibition. This accession provides AP-MS experiment files for the following subset of 18 BRDs: BAZ1B, BRD1, BRD2, BRD3, BRD4, BRD8, BRPF3, BRWD3, CECR2, PHIP, SMARCA2, SP100, SP110, TAF1, TRIM24, TRIM33, TRIM66, ZMYND8, as well as their associated controls (Input, Mock, and SBP-tagged NLS).
HostingRepository	PRIDE
AnnounceDate	2019-12-16
AnnouncementXML	Submission_2019-12-16_05:12:35.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD016700
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Anna Battenhouse
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	Carbamidomethyl
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2019-12-11 05:22:14	ID requested
1	2019-12-12 04:23:50	announced
⏵ 2	2019-12-16 05:12:37	announced	2019-12-16: Updated project metadata.

Kim JJ, Lee SY, Gong F, Battenhouse AM, Boutz DR, Bashyal A, Refvik ST, Chiang CM, Xhemalce B, Paull TT, Brodbelt JS, Marcotte EM, Miller KM, Systematic bromodomain protein screens identify homologous recombination and R-loop suppression pathways involved in genome integrity. Genes Dev, 33(23-24):1751-1774(2019) [pubmed]

submitter keyword: AP-MS, Human, Bromodomain, Chromatin, Homologous Recombination, DNA repair, DNA damage response, R-loops

Kyle M. Miller
contact affiliation	Dept. of Molecular Biosciences, University of Texas at Austin, Texas 78712 USA
contact email	kyle.miller@austin.utexas.edu
lab head
Anna Battenhouse
contact affiliation	The University of Texas at Austin
contact email	abattenhouse@utexas.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/2019/12/PXD016700

PRIDE project URI

• PRIDE
  1. PXD016700
     1. Label: PRIDE project
     2. Name: Affinity Purification experiments for 24 human Bromodomain proteins involved in DNA repair and genome integrity (part 1 of 2).