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PXD053309

PXD053309 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleTDP1 phosphorylation at S61 promotes Top1cc repair via the MUS81-dependent pathway during mitosis
DescriptionTopoisomerase 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.
HostingRepositoryPRIDE
AnnounceDate2024-10-22
AnnouncementXMLSubmission_2024-10-22_06:47:27.913.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterBenu Brata Das
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListphosphorylated residue
InstrumentQ Exactive
Dataset History
RevisionDatetimeStatusChangeLog Entry
02024-06-23 01:35:42ID requested
12024-06-26 01:09:45announced
22024-10-22 06:47:28announced2024-10-22: Updated project metadata.
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: Topoisomerase 1, MiDAS, MUS81, CDK1, TDP1
Contact List
Professor Benu Brata Das
contact affiliationLaboratory 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 emailpcbbd@iacs.res.in
lab head
Benu Brata Das
contact affiliationLaboratory 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 emailpcspc@iacs.res.in
dataset submitter
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Dataset FTP location
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