PXD053309

PXD053309 is an original dataset announced via ProteomeXchange.

Title	TDP1 phosphorylation at S61 promotes Top1cc repair via the MUS81-dependent pathway during mitosis
Description	Topoisomerase 1 (Top1) removes supercoils from DNA during replication and transcription, is critical for mitotic progression to the G1 phase, and ensures DNA topology. Tyrosyl-DNA phosphodiesterase 1 (TDP1) mediates the removal of trapped Top1-DNA covalent complexes (Top1ccs). Here, we identify CDK1-dependent phosphorylation of TDP1 at S61 residue during mitosis. TDP1 defective for S61 phosphorylation (TDP1S61A) is trapped on the mitotic chromosomes, triggering DNA damage and mitotic defects. Moreover, we show that Top1cc repair in mitosis occurs via MUS81-dependent mitotic DNA repair mechanism. Replication stress (RS) induced by Camptothecin (CPT) or Aphidicolin (APH) leads to TDP1S61A enrichment at common fragile sites (CFSs), which over-stimulates MUS81-dependent chromatid breaks, anaphase bridges, and micronuclei, ultimately culminating in 53BP1 nuclear bodies in the G1-phase. Our findings provide a new insight into the cell cycle-dependent regulation of TDP1 dynamics forthe repair of trapped Top1ccs during mitosis that prevents genomic instability following RS.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:47:27.913.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Benu Brata Das
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2024-06-23 01:35:42	ID requested
1	2024-06-26 01:09:45	announced
⏵ 2	2024-10-22 06:47:28	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

submitter keyword: Topoisomerase 1, MiDAS, MUS81, CDK1, TDP1

Professor Benu Brata Das
contact affiliation	Laboratory of Molecular Biology, School of Biological Sciences, Indian Association for the Cultivation of Science, 2A & B, Raja S. C. Mullick Road, Jadavpur, Kolkata-700032, India.
contact email	pcbbd@iacs.res.in
lab head
Benu Brata Das
contact affiliation	Laboratory of Molecular Biology, School of Biological Sciences, Indian Association for the Cultivation of Science, 2A & B, Raja S. C. Mullick Road, Jadavpur, Kolkata-700032, India. Tel: +91 33 2473 4971
contact email	pcspc@iacs.res.in
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD053309
     1. Label: PRIDE project
     2. Name: TDP1 phosphorylation at S61 promotes Top1cc repair via the MUS81-dependent pathway during mitosis