@article{12051,
  abstract     = {Transcription of the ribosomal RNA precursor by RNA polymerase (Pol) I is a major determinant of cellular growth, and dysregulation is observed in many cancer types. Here, we present the purification of human Pol I from cells carrying a genomic GFP fusion on the largest subunit allowing the structural and functional analysis of the enzyme across species. In contrast to yeast, human Pol I carries a single-subunit stalk, and in vitro transcription indicates a reduced proofreading activity. Determination of the human Pol I cryo-EM reconstruction in a close-to-native state rationalizes the effects of disease-associated mutations and uncovers an additional domain that is built into the sequence of Pol I subunit RPA1. This “dock II” domain resembles a truncated HMG box incapable of DNA binding which may serve as a downstream transcription factor–binding platform in metazoans. Biochemical analysis, in situ modelling, and ChIP data indicate that Topoisomerase 2a can be recruited to Pol I via the domain and cooperates with the HMG box domain–containing factor UBF. These adaptations of the metazoan Pol I transcription system may allow efficient release of positive DNA supercoils accumulating downstream of the transcription bubble.},
  author       = {Daiß, Julia L and Pilsl, Michael and Straub, Kristina and Bleckmann, Andrea and Höcherl, Mona and Heiss, Florian B and Abascal-Palacios, Guillermo and Ramsay, Ewan P and Tluckova, Katarina and Mars, Jean-Clement and Fürtges, Torben and Bruckmann, Astrid and Rudack, Till and Bernecky, Carrie A and Lamour, Valérie and Panov, Konstantin and Vannini, Alessandro and Moss, Tom and Engel, Christoph},
  issn         = {2575-1077},
  journal      = {Life Science Alliance},
  keywords     = {Health, Toxicology and Mutagenesis, Plant Science, Biochemistry, Genetics and Molecular Biology (miscellaneous), Ecology},
  number       = {11},
  publisher    = {Life Science Alliance},
  title        = {{The human RNA polymerase I structure reveals an HMG-like docking domain specific to metazoans}},
  doi          = {10.26508/lsa.202201568},
  volume       = {5},
  year         = {2022},
}

@article{11058,
  abstract     = {Nucleoporin 93 (Nup93) expression inversely correlates with the survival of triple-negative breast cancer patients. However, our knowledge of Nup93 function in breast cancer besides its role as structural component of the nuclear pore complex is not understood. Combination of functional assays and genetic analyses suggested that chromatin interaction of Nup93 partially modulates the expression of genes associated with actin cytoskeleton remodeling and epithelial to mesenchymal transition, resulting in impaired invasion of triple-negative, claudin-low breast cancer cells. Nup93 depletion induced stress fiber formation associated with reduced cell migration/proliferation and impaired expression of mesenchymal-like genes. Silencing LIMCH1, a gene responsible for actin cytoskeleton remodeling and up-regulated upon Nup93 depletion, partially restored the invasive phenotype of cancer cells. Loss of Nup93 led to significant defects in tumor establishment/propagation in vivo, whereas patient samples revealed that high Nup93 and low LIMCH1 expression correlate with late tumor stage. Our approach identified Nup93 as contributor of triple-negative, claudin-low breast cancer cell invasion and paves the way to study the role of nuclear envelope proteins during breast cancer tumorigenesis.},
  author       = {Bersini, Simone and Lytle, Nikki K and Schulte, Roberta and Huang, Ling and Wahl, Geoffrey M and HETZER, Martin W},
  issn         = {2575-1077},
  journal      = {Life Science Alliance},
  keywords     = {Health, Toxicology and Mutagenesis, Plant Science, Biochemistry, Genetics and Molecular Biology (miscellaneous), Ecology},
  number       = {1},
  publisher    = {Life Science Alliance},
  title        = {{Nup93 regulates breast tumor growth by modulating cell proliferation and actin cytoskeleton remodeling}},
  doi          = {10.26508/lsa.201900623},
  volume       = {3},
  year         = {2020},
}

