Eldorado - Repositorium der TU Dortmund

Ressourcen aus und für Forschung, Lehre und Studium

Bei diesem Service handelt es sich um das Institutionelle Repositorium der Technischen Universität Dortmund. Hier werden Ressourcen aus und für Lehre, Studium und Forschung gespeichert, erschlossen und der Öffentlichkeit zugänglich gemacht.

Hauptbereiche in Eldorado

Wählen Sie einen Bereich, um dessen Inhalt anzusehen.

Gerade angezeigt 1 - 5 von 9

Fach- und Universitätsübergreifendes 1319
Fakultäten 13897
Graduate School und Graduiertenkollegs 12
Hochschulverwaltung 1250
Sonderforschungsbereiche 1595

Aktuellste Veröffentlichungen

Targeted degradation of USP7 in solid cancer cells reveals distinct effects of deubiquitinase degraders and inhibitors
(Springer Science and Business Media LLC, 2026-05-13) Klink, Nikolas; Urban, Sebastian; Seier, Johanna A.; Adhikari, Bikash; Schwalm, Martin P.; Müller, Juliane; Dorsch, Madeleine; Steinbach, Philine; Jung, Jennifer; Vogt, Markus; Kaschani, Farnusch; Koch, Johannes; Führer, Siska; Kaiser, Markus; Schulze, Nina; Knapp, Stefan; Wolf, Elmar; Paschen, Annette; Grüner, Barbara M.; Gersch, Malte
Proteolysis-targeting chimeras (PROTACs) co-op the ubiquitin system for targeted protein degradation, creating opportunities to interrogate cellular functions of proteins through “chemical knockdown”. However, matched pairs of protein degraders and inhibitors, that possess high specificity and chemical complementarity, for individual components of the ubiquitin system have remained scarce. This includes reagents to modulate activity and abundance of deubiquitinases (DUBs). Here, using an integrated chemical biology approach, we explore cellular functions of the DUB USP7 as a case study by comparing inhibition and degradation in melanoma and pancreatic cancer cells. Through the synthesis of a degrader library, we identify and characterize potent USP7 PROTACs for each cancer type. Proteomic and cellular analyses reveal that selective USP7 degradation modulates both shared and distinct protein sets across both cancers without affecting cell growth. In contrast, prolonged inhibitor treatment induces USP7-independent proteomic and metabolic dysregulation, highlighting important caveats for the cellular use of hydroxypiperidine-based USP7 inhibitors. Collectively, our work provides a comprehensively characterized chemical toolbox to distinguish on-target phenotypes which will aid the understanding of USP7 in malignant diseases. More broadly, our data emphasize the importance of increased specificity via PROTAC-mediated degradation and the potential of this modality to elucidate cell-line specific functions of DUBs.
A role for nucleosome remodellers during resection of deprotected telomeres in yeast
(Public Library of Science (PLoS), 2026-07-10) Deiser, Anja M.; Agar, Caitlyn; Barba Tena, Juan de Dios; Pfander, Boris; Lustig, Arthur J.
DNA double-strand break (DSB) repair pathway choice is strongly influenced by DNA end resection, a process in which the 5′ DNA strand is degraded to generate 3′ single-stranded DNA required for homologous recombination. Although the enzymatic mechanisms of resection have been well defined, its regulation by the dynamic chromatin environment surrounding the DNA break remains less clear. Here, we used the budding yeast cdc13-1 system to analyse DNA end resection after telomere deprotection. Inactivation of Cdc13, a component of the CST (Cdc13–Stn1–Ten1) telomere-capping complex, exposes telomeric DNA ends and triggers a DNA damage response. Using this system, we examined the contribution of long-range resection nucleases and chromatin regulators. Analysis of long-range resection nucleases revealed that the Dna2 nuclease contributes to telomeric processing, particularly in the absence of the exonuclease Exo1. Genetic removal of chromatin regulatory factors showed that H2A.Z, a histone H2A variant incorporated by the SWR1 complex, did not significantly affect resection, whereas depletion of the major nucleosome eviction complexes RSC and SWI/SNF impaired resection after telomere deprotection. Together, these results indicate that nucleosome eviction allows for efficient resection at deprotected telomeres and the analogies to long-range resection at DSBs illustrate the utility of the cdc13-1 system for studying long-range resection in broader context.
Evaluation of dependency blossoms on the Maven Central Repository
(2026-07-13) Jütte, Marvin; Hermann, Ben; Howar, Falk
Reusing code is a common practice by leveraging dependencies, libraries, or frameworks. Yet, there is little to no research targeting framework detection on the Maven Central Repository. One proposed way to detect those frameworks are dependency blossoms consisting of artifacts sharing a common group and the same version. Our goal is to evaluate this definition by providing our own, less strict definition of dependency blossoms. Our approach is based on the assumption that artifacts belonging to the same framework will frequently be published within a small and shared time window. We further propose a pipeline on how to compile the blossoms and implemented parts of the pipeline. In order to test our implementation, we ran it on 10,000 randomly selected releases provided by the Goblin framework dataset. We find that 75% of dependency blossoms, using our approach, consist of a minimum of 1 and up to 6 artifact groups for certainty thresholds of 0.8 or higher. This certainty threshold indicates how certain we are that the given artifact is part of the blossom. Thus, our results indicate that the restriction of dependency blossoms to only consist of artifacts that share a common group and the same version is too strict.
Formkomplementäre Multikomponenten Assemblierung von Niedrigsymmetrischen Co(III)Salphen Koordinationskäfigen
(Wiley, 2024-04-04) Zhang, Bo; Lee, Haeri; Holstein, Julian J.; Clever, Guido H.
Während die metallvermittelte Selbstassemblierung eine beliebte Methode zur Synthese definierter Nanoobjekte ist, wird die Literatur von hochsymmetrischen Strukturen, aufgebaut aus jeweils einer Art von Liganden, dominiert. Die kontrollierte Integration einer Reihe verschiedener Liganden erfordert ausgeklügelte Ansätze, um eine narzisstische Trennung oder die Bildung statistischer Mischungen zu vermeiden. Hier zeigen wir, wie die Kombination von drei strukturleitenden Effekten (metallvermittelte Makrozyklisierung, zusätzliches Anbringen von Brückenliganden und Formkomplementarität) auf der Grundlage von Co(III)salphen-Metallzentren die rationale Synthese von laternenförmigen Käfigen mit bis zu vier differenzierbaren Brücken ermöglicht. Drei neue heteroleptische Koordinationskäfige, basierend auf zweikernigen Co(III)salphen-Makrozyklen, wurden in einer Eintopfreaktion synthetisiert und vollständig charakterisiert, einschließlich Einkristall-Röntgenstrukturanalysen. Einer der Käfige gruppiert zwei gleiche Liganden, ein anderer zwei verschiedene Liganden um einen symmetrischen Co2-Bis-Salphen-Ring. In der komplexesten Struktur ist dieser Ring unsymmetrisch, so dass alle vier Brücken zwischen den beiden Metallzentren unterscheidbar sind. Während sich heteroleptische Assemblies mit Pd(II)-Zentren als dynamisch und vorteilhaft für Käfig-zu-Käfig-Umwandlungen und adaptive Systeme erwiesen haben, werden die hier vorgestellten Käfige auf der Grundlage der kinetisch stabileren Co(III)-Salphen Einheiten für Anwendungen, die eine erhöhte strukturelle und chemische Stabilität erfordern, von Vorteil sein, z.B. in der enzymähnlichen Katalyse und in molekularen Maschinen.
Evolved readers of 5‐Carboxylcytosine CpG dyads reveal a high versatility of the methyl‐CpG‐binding domain for recognition of noncanonical epigenetic marks
(Wiley, 2024-01-29) Kosel, Brinja; Bigler, Katrin; Buchmuller, Benjamin C.; Acharyya, Suchandra R.; Linser, Rasmus; Summerer, Daniel
Mammalian genomes are regulated by epigenetic cytosine (C) modifications in palindromic CpG dyads. Including canonical cytosine 5-methylation (mC), a total of four different 5-modifications can theoretically co-exist in the two strands of a CpG, giving rise to a complex array of combinatorial marks with unique regulatory potentials. While tailored readers for individual marks could serve as versatile tools to study their functions, it has been unclear whether a natural protein scaffold would allow selective recognition of marks that vastly differ from canonical, symmetrically methylated CpGs. We conduct directed evolution experiments to generate readers of 5-carboxylcytosine (caC) dyads based on the methyl-CpG-binding domain (MBD), the widely conserved natural reader of mC. Despite the stark steric and chemical differences to mC, we discover highly selective, low nanomolar binders of symmetric and asymmetric caC-dyads. Together with mutational and modelling studies, our findings reveal a striking evolutionary flexibility of the MBD scaffold, allowing it to completely abandon its conserved mC recognition mode in favour of noncanonical dyad recognition, highlighting its potential for epigenetic reader design.