PXD041638

PXD041638 is an original dataset announced via ProteomeXchange.

Title	FTO suppresses DNA repair by inhibiting PARP1
Description	Maintaining genomic integrity and faithful transmission of genetic information are essential for the survival and proliferation of cells and organisms. DNA damage, which threatens the integrity of the genome, is rapidly sensed and repaired by mechanisms collectively known as DNA damage response in cells. Using an unbiased quantitative proteomic approach, we revealed the interactome of an RNA demethylase FTO (fat mass and obesity-associated protein). We identified a direct interaction with the DNA damage sensor protein PARP1 (poly-ADP-ribose polymerase 1), which dissociates upon ultraviolet (UV) stimulation. FTO inhibits PARP1 catalytic activity and controls its clustering in the nucleolus. Loss of FTO enhances PARP1 enzymatic activity and the rate of PARP1 recruitment to DNA damage sites, thus accelerating DNA repair and, consequently, cell survival. Thus, our study establishes FTO as an endogenous negative regulator of PARP1 and the UV-induced DNA damage response, which has implications for the treatment options of various cancers.
HostingRepository	PRIDE
AnnounceDate	2025-03-26
AnnouncementXML	Submission_2025-03-25_17:08:19.426.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD041638
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Albert Lee
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	biotinylated residue; acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2023-04-18 20:01:49	ID requested
⏵ 1	2025-03-25 17:08:19	announced

10.1038/S41467-025-58309-0;

submitter keyword: PARP1, DNA repair, SILAC,fat mass and obesity-associated protein (FTO), DNA damage

Albert Lee
contact affiliation	Centre for MND Research, Macquarie Medical School, Faculty of Medicine Health and Human Sciences, Macquarie University, North Ryde NSW 2109 Australia
contact email	albert.lee@mq.edu.au
lab head
Albert Lee
contact affiliation	Macquarie University
contact email	albert.lee@mq.edu.au
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD041638
     1. Label: PRIDE project
     2. Name: FTO suppresses DNA repair by inhibiting PARP1