Proteomics

Dataset Information

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Deletion of GSE1 and HDAC1 inactivation alters proteomic profiles and cell cycle control


ABSTRACT: The DNA damage response (DDR) is orchestrated by multiple, tightly regulated signalling events. We discovered that genetic suppressor element 1 (GSE1) forms a complex with the histone deacetylation 1 (HDAC1) / CoREST complex and that loss of GSE1 hampers DDR induction. To investigate how GSE1 and HDAC1 can regulate DDR and whether their mode of action might be overlapping, we performed a proteomic analysis using quantitative mass spectrometry based on the TMTpro 16-plex isobaric labelling technology (Li et al., 2020). We determined global acetylome and phosphorylome profiles in the nearly haploid human cell line HAP1 (Andersson et al, 1987) using WT, GSE1 KO and HDAC1 CI backgrounds and compared patterns between untreated and etoposide-treated (0.1 µM, 6 hrs) cells.

INSTRUMENT(S): Orbitrap Eclipse, Orbitrap Exploris 480

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture, Haploid Cell

SUBMITTER: Wolfgang Reiter  

LAB HEAD: Markus Hartl

PROVIDER: PXD040339 | Pride | 2023-10-23

REPOSITORIES: Pride

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Publications

GSE1 links the HDAC1/CoREST co-repressor complex to DNA damage.

Vcelkova Terezia T   Reiter Wolfgang W   Zylka Martha M   Hollenstein David M DM   Schuckert Stefan S   Hartl Markus M   Seiser Christian C  

Nucleic acids research 20231101 21


Post-translational modifications of histones are important regulators of the DNA damage response (DDR). By using affinity purification mass spectrometry (AP-MS) we discovered that genetic suppressor element 1 (GSE1) forms a complex with the HDAC1/CoREST deacetylase/demethylase co-repressor complex. In-depth phosphorylome analysis revealed that loss of GSE1 results in impaired DDR, ATR signalling and γH2AX formation upon DNA damage induction. Altered profiles of ATR target serine-glutamine motifs  ...[more]

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