- EMDB-39338: Cryo-EM structure of the human DSS1-INTAC complex -
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Entry
Database: EMDB / ID: EMD-39338
Title
Cryo-EM structure of the human DSS1-INTAC complex
Map data
local resolution filtered map using relion
Sample
Complex: DSS1-INTAC-PEC
Protein or peptide: x 12 types
Ligand: x 2 types
Keywords
DSS1 / Integrator / INTAC / TRANSCRIPTION
Function / homology
Function and homology information
U2 snRNA 3'-end processing / meiotic spindle elongation / snRNA 3'-end processing / PP2A-mediated dephosphorylation of key metabolic factors / RNA polymerase II CTD heptapeptide repeat S2 phosphatase activity / RNA polymerase II CTD heptapeptide repeat S7 phosphatase activity / peptidyl-threonine dephosphorylation / regulation of meiotic cell cycle process involved in oocyte maturation / mitotic sister chromatid separation / MASTL Facilitates Mitotic Progression ...U2 snRNA 3'-end processing / meiotic spindle elongation / snRNA 3'-end processing / PP2A-mediated dephosphorylation of key metabolic factors / RNA polymerase II CTD heptapeptide repeat S2 phosphatase activity / RNA polymerase II CTD heptapeptide repeat S7 phosphatase activity / peptidyl-threonine dephosphorylation / regulation of meiotic cell cycle process involved in oocyte maturation / mitotic sister chromatid separation / MASTL Facilitates Mitotic Progression / snRNA processing / protein phosphatase type 2A complex / meiotic sister chromatid cohesion, centromeric / INTAC complex / female meiotic nuclear division / RNA polymerase II CTD heptapeptide repeat S5 phosphatase activity / FAR/SIN/STRIPAK complex / Regulation of glycolysis by fructose 2,6-bisphosphate metabolism / Inhibition of replication initiation of damaged DNA by RB1/E2F1 / regulation of transcription elongation by RNA polymerase II / positive regulation of extrinsic apoptotic signaling pathway in absence of ligand / protein phosphatase regulator activity / protein antigen binding / GABA receptor binding / APC truncation mutants have impaired AXIN binding / AXIN missense mutants destabilize the destruction complex / Truncations of AMER1 destabilize the destruction complex / Hydrolases; Acting on ester bonds; Endoribonucleases producing 3'-phosphomonoesters / Impaired BRCA2 translocation to the nucleus / Impaired BRCA2 binding to SEM1 (DSS1) / ERKs are inactivated / Initiation of Nuclear Envelope (NE) Reformation / Beta-catenin phosphorylation cascade / Signaling by GSK3beta mutants / CTNNB1 S33 mutants aren't phosphorylated / CTNNB1 S37 mutants aren't phosphorylated / CTNNB1 S45 mutants aren't phosphorylated / CTNNB1 T41 mutants aren't phosphorylated / regulation of growth / integrator complex / Co-stimulation by CD28 / RNA polymerase II transcription initiation surveillance / Disassembly of the destruction complex and recruitment of AXIN to the membrane / proteasome regulatory particle, lid subcomplex / protein dephosphorylation / T cell homeostasis / negative regulation of epithelial to mesenchymal transition / Co-inhibition by CTLA4 / cellular response to type I interferon / Platelet sensitization by LDL / Regulation of ornithine decarboxylase (ODC) / Proteasome assembly / protein-serine/threonine phosphatase / Cross-presentation of soluble exogenous antigens (endosomes) / Somitogenesis / negative regulation of glycolytic process through fructose-6-phosphate / ERK/MAPK targets / Homologous DNA Pairing and Strand Exchange / Defective homologous recombination repair (HRR) due to BRCA1 loss of function / Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA1 binding function / Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA2/RAD51/RAD51C binding function / Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA) / Resolution of D-loop Structures through Holliday Junction Intermediates / vascular endothelial cell response to oscillatory fluid shear stress / mesoderm development / protein serine/threonine phosphatase activity / regulation of cell differentiation / positive regulation of NLRP3 inflammasome complex assembly / Impaired BRCA2 binding to RAD51 / regulation of microtubule polymerization / RNA polymerase II transcribes snRNA genes / lateral plasma membrane / DARPP-32 events / chromosome, centromeric region / Presynaptic phase of homologous DNA pairing and strand exchange / negative regulation of hippo signaling / AMPK-induced ERAD and lysosome mediated degradation of PD-L1(CD274) / proteasome assembly / mRNA export from nucleus / GSK3B-mediated proteasomal degradation of PD-L1(CD274) / Cyclin A/B1/B2 associated events during G2/M transition / SPOP-mediated proteasomal degradation of PD-L1(CD274) / regulation of G1/S transition of mitotic cell cycle / Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) / spindle assembly / phosphoprotein phosphatase activity / protein localization to chromatin / RNA endonuclease activity / Ribosome Quality Control (RQC) complex extracts and degrades nascent peptide / Loss of Nlp from mitotic centrosomes / Loss of proteins required for interphase microtubule organization from the centrosome / Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal / Recruitment of mitotic centrosome proteins and complexes / protein tyrosine phosphatase activity / Recruitment of NuMA to mitotic centrosomes / DNA damage checkpoint signaling / Anchoring of the basal body to the plasma membrane / Mitotic Prometaphase / EML4 and NUDC in mitotic spindle formation / Turbulent (oscillatory, disturbed) flow shear stress activates signaling by PIEZO1 and integrins in endothelial cells Similarity search - Function
Journal: Nat Commun / Year: 2025 Title: DSS1 is required for proper Integrator-PP2A function. Authors: Congling Xu / Qian-Xing Zhou / Hai Zheng / Aixia Song / Wen-Ying Zhao / Ting-Ting Xu / Yan Xiong / Yi-Jie Zhang / Zixuan Huang / Yanhui Xu / Jingdong Cheng / Fei Xavier Chen / Abstract: Integrator-PP2A (INTAC) is a highly modular complex orchestrating the transition of paused RNA polymerase II into productive elongation or promoter-proximal premature termination, with its loss ...Integrator-PP2A (INTAC) is a highly modular complex orchestrating the transition of paused RNA polymerase II into productive elongation or promoter-proximal premature termination, with its loss resulting in transcription dysregulation and genome instability. Here, we identify human DSS1-a flexible 70-residue protein found in multiple functionally diverse complexes including the 26S proteasome-as an integral subunit of the INTAC backbone. Structural analysis of DSS1-INTAC, both alone and in association with paused polymerase, demonstrates intimate interactions between DSS1 and the INTAC backbone. We identify tryptophan 39 of DSS1 as being critical for interacting with INTAC and find that its mutation disrupts DSS1's interaction with INTAC, while maintaining DSS1's interaction with the proteasome. This substitution not only impairs INTAC-dependent transcriptional regulation, but also reveals that INTAC is DSS1's major chromatin-bound form. Together, our findings reveal a role for DSS1 in supporting the structure and regulatory functions of INTAC.
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