PXD045353

PXD045353 is an original dataset announced via ProteomeXchange.

Title	The type of DNA damage response after Decitabine treatment depends on the level of DNMT activity
Description	Decitabine and Azacytidine are considered as epigenetic drugs that induce DNA-methyltransferase (DNMT)-DNA crosslinks, resulting in DNA-hypomethylation and -damage. Although they are already applied against myeloid cancers, important aspects of their mode of action remain unknown, highly limiting their clinical potential. Using a combinatorial approach, we reveal that the efficacy profile of both compounds primarily depends on the level of induced DNA-damage. Under low DNMT-activity, only Decitabine has a substantial impact. Conversely, when DNMT-activity is high, toxicity and cellular response to both compounds are dramatically increased, but do not primarily depend on DNA-hypomethylation or RNA-associated processes. By investigating proteome dynamics on chromatin, we show that Decitabine induces a strictly DNMT-dependent multifaceted DNA-damage response based on chromatin-recruitment, but not expression level changes of repair-associated proteins. The choice of DNA-repair pathway herby depends on the severity of Decitabine-induced DNA-lesions. While under moderate DNMT-activity, mismatch (MMR), base-excision (BER) and Fanconi anemia-dependent DNA-repair combined with homologous recombination are activated in response to Decitabine, high DNMT-activity and therefore immense replication stress, induce activation of MMR and BER followed by non-homologous end-joining.
HostingRepository	PRIDE
AnnounceDate	2024-06-19
AnnouncementXML	Submission_2024-06-19_07:43:46.884.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Franziska Traube
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	iodoacetamide derivatized residue
Instrument	Orbitrap Eclipse

Revision	Datetime	Status	ChangeLog Entry
0	2023-09-13 07:17:06	ID requested
⏵ 1	2024-06-19 07:43:47	announced

10.26508/LSA.202302437;

submitter keyword: Spatial proteomics, 5-Aza-2'-deoxycytidine, Protein-DNA crosslinks, Azacytidine

Franziska Traube
contact affiliation	Institute of Biochemistry and Technical Biochemistry Department Biochemistry of Cellular Biomedical Systems University of Stuttgart
contact email	franziska.traube@ibtb.uni-stuttgart.de
lab head
Franziska Traube
contact affiliation	IBTB - University of Stuttgart
contact email	franziska.traube@cup.lmu.de
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/2024/06/PXD045353

PRIDE project URI

• PRIDE
  1. PXD045353
     1. Label: PRIDE project
     2. Name: The type of DNA damage response after Decitabine treatment depends on the level of DNMT activity