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PXD035337-1

PXD035337 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleDual role of PCNA-monoubiquitination in facilitating Fanconi Anemia-mediated interstrand crosslink repair
DescriptionThe Fanconi Anemia (FA) repair pathway governs the repair of highly genotoxic DNA interstrand crosslinks (ICLs) with the assistance of translesion synthesis (TLS), that is facilitated by site-specific monoubiquitination of PCNA (PCNA-Ub) at lysine 164 (K164). Mutation at this residue (K164R) renders mammals hypersensitive to ICLs. Besides the FA pathway, alternative pathways have been associated with ICL repair However, the decision-making between the different pathways remains elusive. To study the dependence and relevance of PCNA-Ub in FA repair and pathway preference, we generated a germline Fancg-/- mouse and intercrossed PcnaK164R/+;Fancg-/+ mice. A compound mutation (KR;FGko) was embryonic lethal with the noted exception of very infrequent escapers. RNAseq of primary double mutant mouse embryonic fibroblasts (MEFs) revealed elevated levels of replication stress-induced checkpoints, which were rescued by Trp53 knockdown. Upon crosslink induction, KR and FGko MEFs displayed a similar phenotype regarding sensitivity, cell cycle arrest, fork progression and accumulation of single stranded DNA.Remarkably, PCNA-Ub excludes the mismatch recognition complex MSH2/MSH6 from being recruited. Our results implicate a dual function of PCNA-Ub in ICL repair: 1. Facilitate TLS opposite the unhooked ICL and 2. simultaneously exclude MSH2/MSH6 recruitment to channel the ICL towards canonical FA repair.
HostingRepositoryPRIDE
AnnounceDate2024-08-09
AnnouncementXMLSubmission_2024-08-09_05:22:17.302.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterOnno Bleijerveld
SpeciesList scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationListmonohydroxylated residue; deamidated residue; iodoacetamide derivatized residue
InstrumentQ Exactive HF-X
Dataset History
RevisionDatetimeStatusChangeLog Entry
02022-07-14 06:18:09ID requested
12024-08-09 05:22:18announced
22024-10-22 06:53:58announced2024-10-22: Updated project metadata.
Publication List
10.1093/pnasnexus/pgae242;
Shah R, Aslam MA, Spanjaard A, de Groot D, Z, ΓΌ, rcher LM, Altelaar M, Hoekman L, Pritchard CEJ, Pilzecker B, van den Berk PCM, Jacobs H, Dual role of proliferating cell nuclear antigen monoubiquitination in facilitating Fanconi anemia-mediated interstrand crosslink repair. PNAS Nexus, 3(7):pgae242(2024) [pubmed]
Keyword List
submitter keyword: LC-MSMS, RIME, interstrand crosslink repair, mouse,dna damage tolerance, mismatch repair, fanconi anemia, PCNA ubiquitination
Contact List
Maarten Altelaar
contact affiliationThe Netherlands Cancer Institute Proteomics Facility, Plesmanlaan 121, 1066CX Amsterdam, The Netherlands; Biomolecular Mass Spectrometry and Proteomics, Utrecht University, The Netherlands
contact emailm.altelaar@nki.nl
lab head
Onno Bleijerveld
contact affiliationThe Netherlands Cancer Institute
contact emailo.bleijerveld@nki.nl
dataset submitter
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