PXD046611

PXD046611 is an original dataset announced via ProteomeXchange.

Title	RAD54L2 mediates a novel mechanism to counter TOP2-DNA adducts
Description	The catalytic cycle of topoisomerase 2 (TOP2) enzymes proceeds via a transient DNA double-strand break (DSB) intermediate termed the TOP2 cleavage complex (TOP2cc), in which the TOP2 protein is covalently bound to DNA. Anti-cancer agents such as etoposide operate by stabilising TOP2ccs, ultimately generating genotoxic TOP2-DNA protein crosslinks that require processing and repair. Here, we identify RAD54L2 as a factor promoting TOP2cc resolution. We demonstrate that RAD54L2 acts through a novel mechanism together with ZNF451 and independent of TDP2. Our work suggests a model wherein RAD54L2 recognises sumoylated-TOP2 and, using its ATPase activity, promotes TOP2cc resolution and prevents DSB exposure. These findings suggest RAD54L2-mediated TOP2cc resolution as a potential mechanism for cancer-therapy resistance and highlight RAD54L2 as an attractive candidate for drug discovery.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:27:30.536.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Petra Beli
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive Plus

Revision	Datetime	Status	ChangeLog Entry
0	2023-11-02 10:19:43	ID requested
1	2024-01-26 10:35:05	announced
⏵ 2	2024-10-22 06:27:32	announced	2024-10-22: Updated project metadata.

D'Alessandro G, Morales-Juarez DA, Richards SL, Nitiss KC, Serrano-Benitez A, Wang J, Thomas JC, Gupta V, Voigt A, Belotserkovskaya R, Goh CG, Bowden AR, Galanty Y, Beli P, Nitiss JL, Zagnoli-Vieira G, Jackson SP, RAD54L2 counters TOP2-DNA adducts to promote genome stability. Sci Adv, 9(49):eadl2108(2023) [pubmed]

10.1126/sciadv.adl2108;

submitter keyword: cancer,TOP2-DNA adducts,Etoposide,RAD54L2

Petra Beli
contact affiliation	Institute of Molecular Biology (IMB), Chromatin Biology & Proteomics, Mainz, Germany Institute of Developmental Biology and Neurobiology (IDN), Johannes Gutenberg-Universität, Mainz, Germany
contact email	p.beli@imb-mainz.de
lab head
Petra Beli
contact affiliation	Institute of Molecular Biology (IMB), Mainz, Germany
contact email	p.beli@imb-mainz.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/2024/01/PXD046611

PRIDE project URI

• PRIDE
  1. PXD046611
     1. Label: PRIDE project
     2. Name: RAD54L2 mediates a novel mechanism to counter TOP2-DNA adducts