PXD048568-1

PXD048568 is an original dataset announced via ProteomeXchange.

Title	Protein UFMylation regulates ribosomal DNA double-stranded break repair
Description	Ribosomal DNA (rDNA) arrays are highly repetitive regions of the genome which encode essential genes required to produce ribosomes. DNA double-stranded breaks (DSBs) generated within rDNA genes elicit a unique cellular response involving robust transcriptional silencing and nucleolar reorganization into ‘cap’ structures at the nucleolar periphery. This process is coordinated by the nucleolar scaffolding protein TCOF1, which functions to recruit the DNA repair proteins NBS1 and TOPBP1 that activate the ATM and ATR kinases, resulting in ribosomal RNA (rRNA) transcriptional silencing and nucleolar segregation. However, the DNA damage and repair response at rDNA arrays remains incompletely understood. Here, we investigate the cellular response to rDNA DSBs using proteomics and genetic CRISPR-Cas9 screening. We show that the protein UFMylation pathway and the HUSH complex are important for cell viability and survival in response to rDNA DSBs, and that the E3 UFM1-ligase UFL1 and its heterodimer DDRGK1 are associated with TCOF1 at nucleolar caps. Loss of UFL1 leads to impaired ATM activation, reduced rRNA transcriptional silencing, and an overall reduction in nucleolar segregation. We identified ATM, UNC45A and SMC6 as UFMylated proteins, in which UFMylation may facilitate ATM activation and segregation of damaged rDNA to the nucleolar periphery. Altogether, our findings provide the first evidence for a role for UFMylation in rDNA DSB repair.
HostingRepository	PRIDE
AnnounceDate	2024-09-16
AnnouncementXML	Submission_2024-09-16_09:58:04.950.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD048568
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Marlene Oeffinger
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2024-01-15 14:09:51	ID requested
⏵ 1	2024-09-16 09:58:05	announced

10.6019/PXD048568;

10.1016/j.celrep.2024.114738;

Panichnantakul P, Aguilar LC, Daynard E, Guest M, Peters C, Vogel J, Oeffinger M, Protein UFMylation regulates early events during ribosomal DNA-damage response. Cell Rep, 43(9):114738(2024) [pubmed]

submitter keyword: TCOF1, UFMylation, hTERT-RPE1, Treacle, nucleolus, ribosomal DNA repair,LC-MSMS

Marlene Oeffinger
contact affiliation	Institut de recherches cliniques de Montréal, Center for Genetic and Neurological Diseases,Montréal, QC, Canada Département de biochimie et médecine moléculaire, Université de Montréal, Montréal, QC, Canada Division of Experimental Medicine, McGill University, Montreal, QC, Canada
contact email	Marlene.Oeffinger@ircm.qc.ca
lab head
Marlene Oeffinger
contact affiliation	Institut de recherches cliniques Montreal (IRCM) Universite de Montreal
contact email	marlene.oeffinger@ircm.qc.ca
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/2024/09/PXD048568

PRIDE project URI

• PRIDE
  1. PXD048568
     1. Label: PRIDE project
     2. Name: Protein UFMylation regulates ribosomal DNA double-stranded break repair