PXD054028-1

PXD054028 is an original dataset announced via ProteomeXchange.

Title	SRBD1, a highly conserved factor required for chromosome individualiza-tion in prophase
Description	Untangling of DNA is crucial for the individualization of sister chromatids to prevent errors in chromosome segregation in mitosis. Topoisomerase IIα (TOP2A) plays a pivotal role in this process, serving as the primary enzyme responsible for decatenating sister chromatids. The loop-extrusion activity of condensins at the onset of mitosis produces tension on catenanes, directing TOP2A activity towards decatenation. Consequently, condensins and topoisomerase collaborate in the individualization of sister chromatids. Through a haplo-genetic screen in human cells, we identified a highly conserved protein, S1 RNA-binding domain-containing protein (SRBD1), to be absolutely essential for sister chromatid segregation in WT cells but not in Condensin II-deficient cells. The anaphase defects observed upon loss of SRBD1 strikingly resemble the mitotic defects observed when decatenation is perturbed by inhibition or depletion of TOP2A. Moreover, SRBD1 localizes at the central axis of mitotic chromatids, akin to condensins and TOP2A. We show that the activity of SRBD1 is most critical during prophase, corresponding to the peak of Condensin II and TOP2A activity. We found that SRBD1 exhibits direct DNA binding activity with a preference for single-stranded DNA, implying its action at specific genomic structures. Indeed, we found that SRBD1 is strongly enriched at genomic loci associated to transcription and DNA repair. Altogether, we propose that SRBD1 acts at such locations to promote directionality of TOP2A and to prevent the formation of difficult-to-resolve DNA structures, thereby averting severe chromosome missegregations, a function that seems anciently conserved.
HostingRepository	PRIDE
AnnounceDate	2025-03-24
AnnouncementXML	Submission_2025-03-24_00:20:54.656.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Liesbeth Hoekman
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; deaminated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2024-07-18 00:50:48	ID requested
⏵ 1	2025-03-24 00:20:55	announced

10.1016/J.CELREP.2025.115443;

submitter keyword: Topoisomerase 2, SRBD1, Condensin, Evosep, Catenanes, Anaphase, LC-MS/MS

Onno Bleijerveld
contact affiliation	Mass Spectrometry and Proteomics Facility, The Netherlands Cancer Institute, Amsterdam, The Netherlands
contact email	o.bleijerveld@nki.nl
lab head
Liesbeth Hoekman
contact affiliation	The Netherlands Cancer Institute, Amsterdam, The Netherlands.
contact email	l.hoekman@nki.nl
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD054028
     1. Label: PRIDE project
     2. Name: SRBD1, a highly conserved factor required for chromosome individualiza-tion in prophase