PXD027252-1

PXD027252 is an original dataset announced via ProteomeXchange.

Title	AUF1 recognizes 8-oxo-guanosine embedded in DNA and stimulates APE1 endoribonuclease activity
Description	The presence of rNMPs embedded in DNA represents a frequent genomic event able to destabilize the DNA backbone and to alter DNA replication and transcription. Usually, rNMPs are excised by RNase H2 and fully repaired by other enzymes belonging to the ribonucleotide excision repair pathway. The existence of modified rNMPs embedded in DNA, including 8-oxo-guanosine (8-oxo-G) and ribose monophosphate abasic site (rAP), have been recently highlighted by several works including ours. While eukaryotic RNase H2 is unable to process rAP and 8-oxo-G embedded in DNA, we demonstrated a role of APE1, a key enzyme of the base excision repair pathway, on these lesions. Notably, though APE1 activity on the repair of rAP sites results as efficient as the canonical dAP site, its incision repair activity on 8-oxo-G is very weak. Therefore, in order to guarantee an efficient repair activity of 8-oxo-G, additional processing mechanisms should be active in cells. In this work, by using an unbiased proteomic approach to isolate proteins able to recognize 8-oxo-G embedded in DNA, we discovered that AUF1 actively and specifically recognize 8-oxo-G and, interestingly, stimulates the APE1 enzymatic activity on this substrate. Although further structural analysis should be performed, it is reasonable that AUF1 facilitates the endoribonuclease activity of APE1 on 8-oxo-G by stabilizing the lesion substrate. Furthermore, by two orthogonal approaches including GST-pulldown and proximity ligation assay, we uncovered a novel protein-protein interaction between AUF1 and APE1. Remarkable, this interaction is modulated by H2O2-treatment, playing a putative biological role during cell response to oxidative stress.
HostingRepository	PRIDE
AnnounceDate	2024-10-17
AnnouncementXML	Submission_2024-10-17_02:47:55.755.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Giovanni Renzone
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; deamidated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2021-07-12 08:18:01	ID requested
⏵ 1	2024-10-17 02:47:56	announced

Malfatti MC, Codrich M, Dalla E, D'Ambrosio C, Storici F, Scaloni A, Tell G, AUF1 Recognizes 8-Oxo-Guanosine Embedded in DNA and Stimulates APE1 Endoribonuclease Activity. Antioxid Redox Signal, 39(7-9):411-431(2023) [pubmed]

10.1089/ars.2022.0105;

submitter keyword: APE1, DNA-binding protein

Andrea Scaloni
contact affiliation	Proteomics, Metabolomics & Mass Spectrometry Laboratory, ISPAAM, NationalResearch Council, Naples, Italy
contact email	andrea.scaloni@ispaam.cnr.it
lab head
Giovanni Renzone
contact affiliation	ISPAAM-CNR
contact email	giovanni.renzone@cnr.it
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2024/10/PXD027252

PRIDE project URI

• PRIDE
  1. PXD027252
     1. Label: PRIDE project
     2. Name: AUF1 recognizes 8-oxo-guanosine embedded in DNA and stimulates APE1 endoribonuclease activity