PXD043990-3

PXD043990 is an original dataset announced via ProteomeXchange.

Title	DNA damage induces nuclear envelope rupture through ATR-mediated phosphorylation of Lamin A/C - Synthetic Peptide
Description	The integrity of the nuclear envelope (NE) is essential to maintain the structural stability of the nucleus. Rupture of the NE has been frequently observed in cancer cells, especially in the context of mechanical challenges, such as physical confinement and migration. However, spontaneous NE rupture events have also been described, without any obvious physical challenges to the cell. The molecular mechanism(s) of these spontaneous NE rupture events remain to be explored. Here, we show that DNA damage and subsequent ATR activation can lead to NE rupture. Upon DNA damage, Lamin A/C is phosphorylated in an ATR-dependent manner, leading to changes in lamina assembly and, ultimately, NE rupture. In addition, we show that cancer cells with intrinsic DNA repair defects undergo frequent events of DNA damage-induced NE rupture, which renders them extremely sensitive to further NE perturbations. Exploiting this NE vulnerability could provide a new angle to complement traditional, DNA damage-based chemotherapy.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:05:19.049.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Vanessa Masson
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2023-07-21 09:40:24	ID requested
1	2023-10-09 08:46:48	announced
2	2023-11-14 08:24:02	announced	2023-11-14: Updated project metadata.
⏵ 3	2024-10-22 06:05:19	announced	2024-10-22: Updated project metadata.

10.1016/J.MOLCEL.2023.09.023;

submitter keyword: ATR, NE vulnerability,Nuclear envelope rupture, HR-deficiency, lamina, Lamin A/C phosphorylation, DNA damage, synthetic lethality

Damarys Loew
contact affiliation	Head of the Curie Institute Mass Spectrometry Platform
contact email	damarys.loew@curie.fr
lab head
Vanessa Masson
contact affiliation	Institut Curie - Centre de Recherche
contact email	vanessa.masson@curie.fr
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/2023/10/PXD043990

PRIDE project URI

• PRIDE
  1. PXD043990
     1. Label: PRIDE project
     2. Name: DNA damage induces nuclear envelope rupture through ATR-mediated phosphorylation of Lamin A/C - Synthetic Peptide