PXD043515-1

PXD043515 is an original dataset announced via ProteomeXchange.

Title	Msc1 is a novel nuclear envelope protein that reinforces the DNA damage response in late mitosis
Description	Precise double-strand break (DSB) signaling and repair is paramount for maintaining genome stability. Homologous recombination (HR) is the chosen DSB repair pathway when cyclin-dependent kinase (CDK) activity is high, as it correlates well with the availability of an intact sister chromatid to be used as a template. However, the late stages of mitosis, anaphase and telophase, are paradoxical scenarios since high CDK levels favor HR repair despite sister chromatids being no longer aligned. To identify factors that specifically are involved in DSB repair in late mitosis, we have now undertaken a comparative proteomic analysis in Saccharomyces cerevisiae and found that Msc1, a poorly characterized protein previously identified as important in meiotic HR, is significantly enriched upon both random and guided DSBs. We further show that the knockout mutant for MSC1 is more sensitive to DSBs in late mitosis, and that msc1Δ has a delayed repair of DBSs as indicated by increased Rad53 hyperphosphorylation, fewer Rad52 repair factories and slower HR completion. We have found that Msc1 is an NE protein that faces the NE lumen and tends to form patches in nuclear halves that contain Rad52 factories. Either depletion or overexpression of Msc1 leads to DSB-independent abnormal nuclear morphologies in late mitosis, including blebbing, compartmentalization and premature signs of karyokinesis. In this regard, one of the two Msc1 orthologs in Schizosaccharomyces pombe, Les1, has been shown to regulate karyokinesis. We discuss how Msc1 may protect the late NE from abnormal events during DSB repair, providing a previously unreported link between NE homeostasis and DSB repair in late mitosis.
HostingRepository	PRIDE
AnnounceDate	2024-08-10
AnnouncementXML	Submission_2024-08-10_12:45:15.999.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	F Butter
SpeciesList	scientific name: Saccharomyces cerevisiae (Baker's yeast); NCBI TaxID: 4932;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2023-07-03 15:48:21	ID requested
⏵ 1	2024-08-10 12:45:16	announced
2	2024-10-22 06:54:24	announced	2024-10-22: Updated project metadata.

10.1016/j.isci.2024.110250;

Medina-Su, á, rez S, Ayra-Plasencia J, P, é, rez-Mart, í, nez L, Butter F, Mach, í, n F, Msc1 is a nuclear envelope protein that reinforces DNA repair in late mitosis. iScience, 27(7):110250(2024) [pubmed]

submitter keyword: LC-MS/MS

Falk Butter
contact affiliation	Institute of Molecular Biology (IMB)
contact email	f.butter@imb.de
lab head
F Butter
contact affiliation	Quantitative Proteomics Institute of Molecular Biology (IMB)
contact email	f.butter@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/2024/08/PXD043515

PRIDE project URI

• PRIDE
  1. PXD043515
     1. Label: PRIDE project
     2. Name: Msc1 is a novel nuclear envelope protein that reinforces the DNA damage response in late mitosis