Proteomics

Dataset Information

0

A site-specific analysis of the ADP-Ribosylome unveils Homogeneous Serine ADP-Ribosylation across wild-type and BRCA-mutant Breast Cancer cell lines


ABSTRACT: ADP-ribosylation (ADPr) signaling plays a crucial role in the DNA damage response. Inhibitors against the main enzyme catalyzing ADPr after DNA damage – PARP1 – are used as targeted therapies against breast cancers with BRCA1/2 mutations. However, development of resistance to PARP inhibitors (PARPi) is a major obstacle in treating patients. To better understand the role of ADPr in PARPi sensitivity, we used Liquid Chromatography-Mass Spectrometry (LC-MS) for systems level analysis of the ADP-ribosylome in six breast cancer cell lines with different PARPi sensitivities. We identified 1632 sites on 777 proteins, primarily on serine residues, with a high site overlap of DNA damage-related proteins across all cell lines, demonstrating high conservation in ADPr signaling after DNA damage. We furthermore observed site-specific differences in ADPr intensities in PARPi-sensitive BRCA mutants, and unique ADPr sites in PARPi-resistant BRCA mutant cells, which we notably show to have low PARG levels and longer PARP1 ADPr chains.

INSTRUMENT(S): Orbitrap Fusion Lumos, Orbitrap Exploris 480

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Permanent Cell Line Cell, Cell Culture

DISEASE(S): Breast Cancer

SUBMITTER: Holda Anagho  

LAB HEAD: Michael Lund Nielsen

PROVIDER: PXD047613 | Pride | 2024-08-02

REPOSITORIES: Pride

Similar Datasets

2021-11-02 | PXD027454 | Pride
2023-08-30 | PXD040898 | Pride
2020-11-17 | PXD020589 | Pride
2016-12-22 | PXD005462 | Pride
2024-06-28 | PXD049682 | Pride
2023-05-26 | PXD036512 | Pride
2024-05-08 | PXD048274 | Pride
2020-01-27 | PXD011690 | Pride
2023-09-08 | PXD038822 | Pride
2018-08-29 | PXD009208 | Pride