---
_id: '12051'
abstract:
- lang: eng
  text: 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.
acknowledgement: "The authors especially thank Philip Gunkel for his contribution.
  We thank all\r\npast and present members of the Engel lab, Achim Griesenbeck, Colyn
  Crane-\r\nRobinson, Christophe Lotz, Marlene Vayssieres, Klaus Grasser, Herbert
  Tschochner, and Philipp Milkereit for help and discussion; Gerhard Lehmann and Nobert
  Eichner for IT support; Joost Zomerdijk for UBF-constructs, Volker Cordes for the
  Hela P2 cell line; Remco Sprangers for shared cell culture; Dina Grohmann and the
  Archaea Center for fermentation; and Thomas\r\nDresselhaus for access to fluorescence
  microscopes. This work was in part supported by the Emmy-Noether Programm (DFG grant
  no. EN 1204/1-1 to C Engel) of the German Research Council and Collaborative Research
  Center 960 (TP-A8 to C Engel)."
article_number: e202201568
article_processing_charge: No
article_type: original
author:
- first_name: Julia L
  full_name: Daiß, Julia L
  last_name: Daiß
- first_name: Michael
  full_name: Pilsl, Michael
  last_name: Pilsl
- first_name: Kristina
  full_name: Straub, Kristina
  last_name: Straub
- first_name: Andrea
  full_name: Bleckmann, Andrea
  last_name: Bleckmann
- first_name: Mona
  full_name: Höcherl, Mona
  last_name: Höcherl
- first_name: Florian B
  full_name: Heiss, Florian B
  last_name: Heiss
- first_name: Guillermo
  full_name: Abascal-Palacios, Guillermo
  last_name: Abascal-Palacios
- first_name: Ewan P
  full_name: Ramsay, Ewan P
  last_name: Ramsay
- first_name: Katarina
  full_name: Tluckova, Katarina
  id: 4AC7D980-F248-11E8-B48F-1D18A9856A87
  last_name: Tluckova
- first_name: Jean-Clement
  full_name: Mars, Jean-Clement
  last_name: Mars
- first_name: Torben
  full_name: Fürtges, Torben
  last_name: Fürtges
- first_name: Astrid
  full_name: Bruckmann, Astrid
  last_name: Bruckmann
- first_name: Till
  full_name: Rudack, Till
  last_name: Rudack
- first_name: Carrie A
  full_name: Bernecky, Carrie A
  id: 2CB9DFE2-F248-11E8-B48F-1D18A9856A87
  last_name: Bernecky
  orcid: 0000-0003-0893-7036
- first_name: Valérie
  full_name: Lamour, Valérie
  last_name: Lamour
- first_name: Konstantin
  full_name: Panov, Konstantin
  last_name: Panov
- first_name: Alessandro
  full_name: Vannini, Alessandro
  last_name: Vannini
- first_name: Tom
  full_name: Moss, Tom
  last_name: Moss
- first_name: Christoph
  full_name: Engel, Christoph
  last_name: Engel
citation:
  ama: Daiß JL, Pilsl M, Straub K, et al. The human RNA polymerase I structure reveals
    an HMG-like docking domain specific to metazoans. <i>Life Science Alliance</i>.
    2022;5(11). doi:<a href="https://doi.org/10.26508/lsa.202201568">10.26508/lsa.202201568</a>
  apa: Daiß, J. L., Pilsl, M., Straub, K., Bleckmann, A., Höcherl, M., Heiss, F. B.,
    … Engel, C. (2022). The human RNA polymerase I structure reveals an HMG-like docking
    domain specific to metazoans. <i>Life Science Alliance</i>. Life Science Alliance.
    <a href="https://doi.org/10.26508/lsa.202201568">https://doi.org/10.26508/lsa.202201568</a>
  chicago: Daiß, Julia L, Michael Pilsl, Kristina Straub, Andrea Bleckmann, Mona Höcherl,
    Florian B Heiss, Guillermo Abascal-Palacios, et al. “The Human RNA Polymerase
    I Structure Reveals an HMG-like Docking Domain Specific to Metazoans.” <i>Life
    Science Alliance</i>. Life Science Alliance, 2022. <a href="https://doi.org/10.26508/lsa.202201568">https://doi.org/10.26508/lsa.202201568</a>.
  ieee: J. L. Daiß <i>et al.</i>, “The human RNA polymerase I structure reveals an
    HMG-like docking domain specific to metazoans,” <i>Life Science Alliance</i>,
    vol. 5, no. 11. Life Science Alliance, 2022.
  ista: Daiß JL, Pilsl M, Straub K, Bleckmann A, Höcherl M, Heiss FB, Abascal-Palacios
    G, Ramsay EP, Tluckova K, Mars J-C, Fürtges T, Bruckmann A, Rudack T, Bernecky
    C, Lamour V, Panov K, Vannini A, Moss T, Engel C. 2022. The human RNA polymerase
    I structure reveals an HMG-like docking domain specific to metazoans. Life Science
    Alliance. 5(11), e202201568.
  mla: Daiß, Julia L., et al. “The Human RNA Polymerase I Structure Reveals an HMG-like
    Docking Domain Specific to Metazoans.” <i>Life Science Alliance</i>, vol. 5, no.
    11, e202201568, Life Science Alliance, 2022, doi:<a href="https://doi.org/10.26508/lsa.202201568">10.26508/lsa.202201568</a>.
  short: J.L. Daiß, M. Pilsl, K. Straub, A. Bleckmann, M. Höcherl, F.B. Heiss, G.
    Abascal-Palacios, E.P. Ramsay, K. Tluckova, J.-C. Mars, T. Fürtges, A. Bruckmann,
    T. Rudack, C. Bernecky, V. Lamour, K. Panov, A. Vannini, T. Moss, C. Engel, Life
    Science Alliance 5 (2022).
date_created: 2022-09-06T18:45:23Z
date_published: 2022-09-01T00:00:00Z
date_updated: 2024-10-21T06:01:48Z
day: '01'
ddc:
- '570'
department:
- _id: CaBe
doi: 10.26508/lsa.202201568
external_id:
  isi:
  - '000972702600001'
file:
- access_level: open_access
  checksum: 4201d876a3e5e8b65e319d03300014ad
  content_type: application/pdf
  creator: dernst
  date_created: 2022-09-08T06:41:14Z
  date_updated: 2022-09-08T06:41:14Z
  file_id: '12062'
  file_name: 2022_LifeScienceAlliance_Daiss.pdf
  file_size: 3183129
  relation: main_file
  success: 1
file_date_updated: 2022-09-08T06:41:14Z
has_accepted_license: '1'
intvolume: '         5'
isi: 1
issue: '11'
keyword:
- Health
- Toxicology and Mutagenesis
- Plant Science
- Biochemistry
- Genetics and Molecular Biology (miscellaneous)
- Ecology
language:
- iso: eng
month: '09'
oa: 1
oa_version: Published Version
publication: Life Science Alliance
publication_identifier:
  issn:
  - 2575-1077
publication_status: published
publisher: Life Science Alliance
quality_controlled: '1'
scopus_import: '1'
status: public
title: The human RNA polymerase I structure reveals an HMG-like docking domain specific
  to metazoans
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 5
year: '2022'
...
---
_id: '11058'
abstract:
- lang: eng
  text: 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.
article_number: e201900623
article_processing_charge: No
article_type: original
author:
- first_name: Simone
  full_name: Bersini, Simone
  last_name: Bersini
- first_name: Nikki K
  full_name: Lytle, Nikki K
  last_name: Lytle
- first_name: Roberta
  full_name: Schulte, Roberta
  last_name: Schulte
- first_name: Ling
  full_name: Huang, Ling
  last_name: Huang
- first_name: Geoffrey M
  full_name: Wahl, Geoffrey M
  last_name: Wahl
- first_name: Martin W
  full_name: HETZER, Martin W
  id: 86c0d31b-b4eb-11ec-ac5a-eae7b2e135ed
  last_name: HETZER
  orcid: 0000-0002-2111-992X
citation:
  ama: Bersini S, Lytle NK, Schulte R, Huang L, Wahl GM, Hetzer M. Nup93 regulates
    breast tumor growth by modulating cell proliferation and actin cytoskeleton remodeling.
    <i>Life Science Alliance</i>. 2020;3(1). doi:<a href="https://doi.org/10.26508/lsa.201900623">10.26508/lsa.201900623</a>
  apa: Bersini, S., Lytle, N. K., Schulte, R., Huang, L., Wahl, G. M., &#38; Hetzer,
    M. (2020). Nup93 regulates breast tumor growth by modulating cell proliferation
    and actin cytoskeleton remodeling. <i>Life Science Alliance</i>. Life Science
    Alliance. <a href="https://doi.org/10.26508/lsa.201900623">https://doi.org/10.26508/lsa.201900623</a>
  chicago: Bersini, Simone, Nikki K Lytle, Roberta Schulte, Ling Huang, Geoffrey M
    Wahl, and Martin Hetzer. “Nup93 Regulates Breast Tumor Growth by Modulating Cell
    Proliferation and Actin Cytoskeleton Remodeling.” <i>Life Science Alliance</i>.
    Life Science Alliance, 2020. <a href="https://doi.org/10.26508/lsa.201900623">https://doi.org/10.26508/lsa.201900623</a>.
  ieee: S. Bersini, N. K. Lytle, R. Schulte, L. Huang, G. M. Wahl, and M. Hetzer,
    “Nup93 regulates breast tumor growth by modulating cell proliferation and actin
    cytoskeleton remodeling,” <i>Life Science Alliance</i>, vol. 3, no. 1. Life Science
    Alliance, 2020.
  ista: Bersini S, Lytle NK, Schulte R, Huang L, Wahl GM, Hetzer M. 2020. Nup93 regulates
    breast tumor growth by modulating cell proliferation and actin cytoskeleton remodeling.
    Life Science Alliance. 3(1), e201900623.
  mla: Bersini, Simone, et al. “Nup93 Regulates Breast Tumor Growth by Modulating
    Cell Proliferation and Actin Cytoskeleton Remodeling.” <i>Life Science Alliance</i>,
    vol. 3, no. 1, e201900623, Life Science Alliance, 2020, doi:<a href="https://doi.org/10.26508/lsa.201900623">10.26508/lsa.201900623</a>.
  short: S. Bersini, N.K. Lytle, R. Schulte, L. Huang, G.M. Wahl, M. Hetzer, Life
    Science Alliance 3 (2020).
date_created: 2022-04-07T07:44:18Z
date_published: 2020-01-01T00:00:00Z
date_updated: 2024-10-14T11:18:41Z
day: '01'
ddc:
- '570'
doi: 10.26508/lsa.201900623
extern: '1'
external_id:
  pmid:
  - '31959624'
file:
- access_level: open_access
  checksum: 3bf33e7e93bef7823287807206b69b38
  content_type: application/pdf
  creator: dernst
  date_created: 2022-04-08T07:33:01Z
  date_updated: 2022-04-08T07:33:01Z
  file_id: '11137'
  file_name: 2020_LifeScienceAlliance_Bersini.pdf
  file_size: 2653960
  relation: main_file
  success: 1
file_date_updated: 2022-04-08T07:33:01Z
has_accepted_license: '1'
intvolume: '         3'
issue: '1'
keyword:
- Health
- Toxicology and Mutagenesis
- Plant Science
- Biochemistry
- Genetics and Molecular Biology (miscellaneous)
- Ecology
language:
- iso: eng
month: '01'
oa: 1
oa_version: Published Version
pmid: 1
publication: Life Science Alliance
publication_identifier:
  issn:
  - 2575-1077
publication_status: published
publisher: Life Science Alliance
quality_controlled: '1'
scopus_import: '1'
status: public
title: Nup93 regulates breast tumor growth by modulating cell proliferation and actin
  cytoskeleton remodeling
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 3
year: '2020'
...
---
_id: '6161'
abstract:
- lang: eng
  text: 'The tra-1 gene is a terminal regulator of somatic sex in Caenorhabditis elegans:
    high tra-1 activity elicits female development, low tra-1 activity elicits male
    development. To investigate the function and evolution of tra- 1, we examined
    the tra-1 gene from the closely related nematode C. briggsae. Ce-tra-1 and Cb-tra-1
    are unusually divergent. Each gene generates two transcripts, but only one of
    these is present in both species. This common transcript encodes TRA-1A, which
    shows only 44% amino acid identity between the species, a figure much lower than
    that for previously compared genes. A Cb-tra-1 transgene rescues many tissues
    of tra-1(null) mutants of C. elegans but not the somatic gonad or germ line. This
    transgene also causes nongonadal feminization of XO animals, indicating incorrect
    sexual regulation. Alignment of Ce-TRA-1A and Cb-TRA-1A defined several conserved
    regions likely to be important for tra-1 function. The phenotype differences between
    Ce-tra- 1(null) mutants rescued by Cb-tra-1 transgenes and wild-type C. elegans
    indicate significant divergence of regulatory regions. These molecular and functional
    studies suggest that evolution of sex determination in nematodes is rapid and
    genetically complex.'
author:
- first_name: Mario
  full_name: de Bono, Mario
  id: 4E3FF80E-F248-11E8-B48F-1D18A9856A87
  last_name: de Bono
  orcid: 0000-0001-8347-0443
- first_name: J.
  full_name: Hodgkin, J.
  last_name: Hodgkin
citation:
  ama: 'de Bono M, Hodgkin J. Evolution of sex determination in Caenorhabditis: Unusually
    high divergence of tra-1 and its functional consequences. <i>Genetics</i>. 1996;144(2):587-595.'
  apa: 'de Bono, M., &#38; Hodgkin, J. (1996). Evolution of sex determination in Caenorhabditis:
    Unusually high divergence of tra-1 and its functional consequences. <i>Genetics</i>.
    Genetics Society of America.'
  chicago: 'Bono, Mario de, and J. Hodgkin. “Evolution of Sex Determination in Caenorhabditis:
    Unusually High Divergence of Tra-1 and Its Functional Consequences.” <i>Genetics</i>.
    Genetics Society of America, 1996.'
  ieee: 'M. de Bono and J. Hodgkin, “Evolution of sex determination in Caenorhabditis:
    Unusually high divergence of tra-1 and its functional consequences,” <i>Genetics</i>,
    vol. 144, no. 2. Genetics Society of America, pp. 587–595, 1996.'
  ista: 'de Bono M, Hodgkin J. 1996. Evolution of sex determination in Caenorhabditis:
    Unusually high divergence of tra-1 and its functional consequences. Genetics.
    144(2), 587–595.'
  mla: 'de Bono, Mario, and J. Hodgkin. “Evolution of Sex Determination in Caenorhabditis:
    Unusually High Divergence of Tra-1 and Its Functional Consequences.” <i>Genetics</i>,
    vol. 144, no. 2, Genetics Society of America, 1996, pp. 587–95.'
  short: M. de Bono, J. Hodgkin, Genetics 144 (1996) 587–595.
date_created: 2019-03-21T11:50:37Z
date_published: 1996-10-01T00:00:00Z
date_updated: 2021-01-12T08:06:28Z
day: '01'
extern: '1'
external_id:
  pmid:
  - '8889522'
intvolume: '       144'
issue: '2'
keyword:
- amino acid sequence
- article
- caenorhabditis elegans
- evolution
- genetic variability
- nonhuman
- priority journal
- sex determination
- Amino Acid Sequence
- Animals
- Animals
- Genetically Modified
- Base Sequence
- Caenorhabditis
- Caenorhabditis elegans
- Caenorhabditis elegans Proteins
- DNA
- Helminth
- DNA-Binding Proteins
- Evolution
- Molecular
- Female
- Helminth Proteins
- Membrane Proteins
- Molecular Sequence Data
- Mutagenesis
- RNA
- Messenger
- Sequence Homology
- Amino Acid
- Sex Determination (Analysis)
- Transcription Factors
- Transgenes
- Turner Syndrome
- Animalia
- Caenorhabditis
- Caenorhabditis briggsae
- Caenorhabditis elegans
- Nematoda
language:
- iso: eng
main_file_link:
- open_access: '1'
  url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1207552/
month: '10'
oa: 1
oa_version: Published Version
page: 587-595
pmid: 1
publication: Genetics
publication_identifier:
  issn:
  - '00166731'
publication_status: published
publisher: Genetics Society of America
quality_controlled: '1'
status: public
title: 'Evolution of sex determination in Caenorhabditis: Unusually high divergence
  of tra-1 and its functional consequences'
type: journal_article
user_id: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87
volume: 144
year: '1996'
...