PXD017807

PXD017807 is an original dataset announced via ProteomeXchange.

Title	DELTEX2 C-terminal domain recruits ADP-ribosylated DNA damage repair proteins for ubiquitination.
Description	Crosstalk between ubiquitination and ADP-ribosylation regulates spatio-temporal recruitment of key players during DNA damage repair (DDR). The Deltex family of ubiquitin ligases (DTX1–4 and DTX3L), are characterized by a RING domain followed by a C-terminal domain (DTC) of unknown function; four Deltex proteins have other domains or partner proteins for binding poly-ADP-ribose (PAR), suggesting a role for these proteins in mediating crosstalk between ubiquitination and ADP-ribosylation. Here, we use two label-free mass spectrometry techniques to identify substrates of human DTX2 and demonstrate that DDR proteins are abundant in the DTX2 interactome. Using a combination of structural, biochemical and cell-based techniques, we show that: 1) the DTC domain binds the ADP-ribose moiety of ADP-ribosylated proteins; 2) the DTC domain recruits ADP-ribosylated DDR proteins for ubiquitination; and 3) the efficiency of DDR depends on this function of the DTC domain in DTX2. These findings uncover a new ADP-ribose-binding domain that facilitates PAR-dependent ubiquitination.
HostingRepository	PRIDE
AnnounceDate	2021-09-09
AnnouncementXML	Submission_2021-09-08_18:55:20.793.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Sergio Lilla
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	ubiquitination signature dipeptidyl lysine; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2020-03-02 01:52:34	ID requested
⏵ 1	2021-09-08 18:55:21	announced

Ahmed SF, Buetow L, Gabrielsen M, Lilla S, Chatrin C, Sibbet GJ, Zanivan S, Huang DT, DELTEX2 C-terminal domain recognizes and recruits ADP-ribosylated proteins for ubiquitination. Sci Adv, 6(34):(2020) [pubmed]

submitter keyword: DTX, Deltex C-terminal domain, PARylation-dependent ubiquitination, PAR-binding domain, DNA damage

Sara Rossana Zanivan
contact affiliation	CRUK Beatson Institute, Switchback Road, Glasgow G61 1BD, UK.
contact email	s.zanivan@beatson.gla.ac.uk
lab head
Sergio Lilla
contact affiliation	Proteomics
contact email	s.lilla@beatson.gla.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD017807
     1. Label: PRIDE project
     2. Name: DELTEX2 C-terminal domain recruits ADP-ribosylated DNA damage repair proteins for ubiquitination.