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Downstream Target Screening of TopBP1 in differentiated HPV-positive keratinocytes

ABSTRACT: TopBP1 is more than a DNA damage factor. The knockdown indicates it could have transcriptional regulatory function and we validated this by examining E2F1/p73 pathway.

ORGANISM(S): Homo sapiens

PROVIDER: GSE122018 | GEO | 2018/11/01

REPOSITORIES: GEO

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Downstream Target Screening of TopBP1 in differentiated HPV-positive keratinocytes

Project description:Downstream Target Screening of TopBP1 in differentiated HPV-positive keratinocytes

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TopBP1 associated with RNA in HEK293T cells

Project description:We report the TopBP1 associated with RNA via using sequencing of RNA isolated by PAR-CLIP.

2022-09-23 | GSE213073 | GEO

TOPBP1 Shapes XY Silencing Dynamics during Meiosis to Ensure Male Fertility

Project description:TOPBP1 and other DNA damage response proteins play an important role in meiotic sex chromosome inactivation. We investigate a mutant mouse with a mutation in the BRCT5 domain of TOPBP1 and use single-cell RNA-seq to investigate the effect of the mutation on XY silencing.

2024-02-09 | GSE232588 | GEO

TopBP1 controls conventional dendritic cell development and Flt3L-driven cDC1 differentiation via PU.1 and IRF8

Project description:DNA topoisomerase II-binding protein 1 (TopBP1) plays a vital role in V(D)J recombination during B and T cell development. However, its role in the development of conventional dendritic cells (cDCs) remains unexplored. Mice with DC-specific depletion of TopBP1 (TopBP1cKO) showed accelerated tumor progression due to impaired anti-tumor immunity, characterized by cDC deficiency and pre-DC accumulation. Notably, Flt3 ligand (Flt3L)-mediated tumor immunotherapy was ineffective in TopBP1cKO tumor-bearing mice. Our study demonstrates that TopBP1 is required not only for the steady-state differentiation of total cDCs, including both cDC1 and cDC2, but also for the terminal differentiation of XCR1⁻CD24⁺ emergency progenitors (EPs; CD11c⁺cKit⁺) into XCR1⁺CD24⁺ cDC1s in response to Flt3L. Furthermore, we revealed that TopBP1 directly interacts with PU.1 and IRF8, key transcription factors (TFs) required for cDC development, triggering the expression of their downstream target genes. These findings identify TopBP1 as a crucial factor for cDC development and Flt3L-driven EP differentiation into cDC1s, revealing that the function of key TFs for cDC development is mediated via interaction with TopBP1. Our work underscores the importance of TopBP1 in promoting cDC development and the therapeutic efficacy of Flt3L-mediated tumor immunotherapy.

2026-02-26 | GSE300836 | GEO

TopBP1 controls conventional dendritic cell development and Flt3L-driven cDC1 differentiation via PU.1 and IRF8 [ChIP-Seq]

2025-12-16 | GSE301438 | GEO

Mass spectrometry analysis of the differential binding proteins of TOPBP1/wt and TOPBP1/K250A

Project description:Mass spectrometry analysis of the differential binding proteins of TOPBP1/wt and TOPBP1/K250A.

2022-02-08 | PXD031501 |

TopBP1 associated with RNA in HEK293T cells

Project description:TopBP1 associated with RNA in HEK293T cells

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CIP2A-TOPBP1 Interaction in Human Mitotic Cells

Project description:We investigate the implications of DNA double strand breaks in the human genome, regarding the progression and treatment of various cancer types. During mitosis, the canonical DNA repair mechanisms are suspended while broken chromosomes get temporarily stabilized through so-called adapter proteins. We already knew that TOPBP1 is involved in that process and recently, we identified another Protein which recruits TOPBP1 to sites of damage. After mapping the interaction site on TOPBP1 we attempted to pull down CIP2A using a fragment of the binding domain, followed by chromatography-tandem-mass spectrometry analysis, the results of which we share in this upload.

2022-07-19 | PXD034100 | Pride

Confirmation of replication interactome of TopBP1 using proximity-dependent biotinylation MS

Project description:Goal of the Experiment is to confirm the replication interactome of TopBP1 using stabile 293 FlpIn cell lines expressing TopBP1 adapter fused to APEX2. Proteins in its close proximity will become biotinylated by APEX2, thereby enabling the pulldown of biotinylated proteins and thus, replication involved substrates of TopBP1

2024-05-21 | PXD040000 | Pride

MDC1 interacts with TOPBP1 to maintain chromosomal stability during mitosis

Project description:MDC1 is a large, modular phospho-protein scaffold that mediates recruitment of signaling and repair complexes to sites of DNA double-strand breaks (DSBs). MDC1 is anchored to damaged chromatin through interaction of its C-terminal BRCT-repeat domain with phosphorylated H2AX (γH2AX), where it recruits downstream factors via direct phosphorylation-dependent protein-protein interactions. Here, using unbiased proteomic analyses we identify a highly conserved protein interaction surface near the MDC1 N-terminus for the DNA damage response protein TOPBP1. We show that TOPBP1 directly binds to two residues in MDC1 that are phosphorylated by CK2. Interestingly, we find that TOPBP1 recruitment to DSBs depends on direct interaction with MDC1 only during mitosis. Furthermore, we demonstrate that disrupting MDC1-TOPBP1 binding causes hypersensitivity to ionizing radiation in mitosis, as well as increased micronuclei and chromosomal instability. Thus, our results highlight an important and hitherto unnoticed function for MDC1 and TOPBP1 in maintaining genome stability during cell division.

2019-03-25 | PXD011850 | Pride

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