DELTEX2 C-terminal domain recruits ADP-ribosylated DNA damage repair proteins for ubiquitination.

ABSTRACT: 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.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Embryonic Cell

DISEASE(S): Disease Free

SUBMITTER: Sergio Lilla  

LAB HEAD: Sara Rossana Zanivan

PROVIDER: PXD017807 | Pride | 2021-09-09

REPOSITORIES: Pride