Article
Multidisciplinary Sciences
Anita Lombardi, Lavinia Arseni, Roberta Carriero, Emmanuel Compe, Elena Botta, Debora Ferri, Martina Ugge, Giuseppe Biamonti, Fiorenzo A. Peverali, Silvia Bione, Donata Orioli
Summary: PS-TTD and XP are rare monogenic disorders caused by mutations in the ERCC2/XPD or ERCC3/XPB genes, with XPD and XPB proteins playing key roles in the TFIIH complex. Mutations affecting TFIIH DNA repair activity are responsible for XP, while those impacting transcription result in TTD.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Multidisciplinary Sciences
Kolesnikova Olga, Zachayus Amelie, Pichard Simon, Osz Judit, Rochel Natacha, Rossolillo Paola, Kolb-Cheynel Isabelle, Troffer-Charlier Nathalie, Compe Emmanuel, Bensaude Olivier, Berger Imrev, Poterszman Arnaud
Summary: The Baculovirus/insect cell expression system is a powerful technology for reconstituting eukaryotic macromolecular assemblies. We have established an open source multigene-expression toolbox using homologous recombination, which simplifies the generation of recombinant baculoviruses into a single-step procedure and shortens the time from cloning to protein production.
SCIENTIFIC REPORTS
(2022)
Article
Multidisciplinary Sciences
Shintaro Aibara, Sandra Schilbach, Patrick Cramer
Summary: The initiation of transcription is a crucial step in the regulation of gene activity during mammalian cell differentiation and development. The high-resolution cryo-electron microscopy structure of the human pre-initiation complex provides insight into the mechanisms of DNA opening and transcription initiation.
Article
Biochemistry & Molecular Biology
Inwha Baek, Larry J. Friedman, Jeff Gelles, Stephen Buratowski
Summary: Research shows that in activator-dependent PIC assembly, RNA Pol II, TFIIF, and TFIIE can preassemble on enhancer-bound activators, and multiple RNA Pol II complexes can simultaneously bind to form a localized cluster, while TFIIH binding is unique and depends on the basal promoter.
Article
Biochemistry & Molecular Biology
Sandra Schilbach, Shintaro Aibara, Christian Dienemann, Frauke Grabbe, Patrick Cramer
Summary: This study reveals the high-resolution structure of the transcription initiation complex and the mechanism of DNA opening, crucial for promoter-initiated transcription. TFIIE facilitates initiation by supporting the clamp head loop and regulating the TFIIH translocase.
Article
Multidisciplinary Sciences
Srinivasan Rengachari, Sandra Schilbach, Shintaro Aibara, Christian Dienemann, Patrick Cramer
Summary: Mediator is a conserved coactivator complex involved in the regulated initiation of transcription at eukaryotic genes. It interacts with transcriptional activators to stimulate RNA polymerase II phosphorylation and promoter escape. The complex structure involves various modules that can affect the activity conformation of CDK7 kinase.
Article
Virology
Luisa Mori, Katharine Jenike, Yang-Hui Jimmy Yeh, Benoit Lacombe, Chuan Li, Adam J. Getzler, Sonia Mediouni, Michael E. Cameron, Matthew E. Pipkin, Ya -Chi Ho, Bertha Cecilia Ramirez, Susana T. Valente
Summary: Spironolactone (SP), an FDA approved aldosterone antagonist, inhibits HIV transcription and blocks reactivation from latency by rapidly degrading a host transcription factor subunit, XPB. Long-term SP treatment does not affect cellular viability, cell cycle progression, or global cellular transcription. SP alone blocks HIV transcription in the absence of ART but does not delay rebound upon drug removal, as XPB rapidly reemerges.
JOURNAL OF VIROLOGY
(2021)
Article
Cell Biology
Yuqian Zhu, Dandan Song, Juan Guo, Jiacheng Jin, Ying Tao, Zheng Zhang, Feng Xu, Qi He, Xiao Li, Chunkang Chang, Lingyun Wu
Summary: The study found that U2AF1 mutations are associated with poor prognosis in MDS and AML patients, significantly inhibiting cell proliferation and inducing cellular apoptosis in cell models. The results showed that U2AF1 mutations promoted FOXO3a-dependent apoptosis and NLRP3 inflammasome activation, leading to pyroptotic cell death. FOXO3a was identified as the key molecule on which these pathways converge.
CELL DEATH & DISEASE
(2021)
Article
Biochemistry & Molecular Biology
Qianying Hu, Na Zhang, Tingting Sui, Guanlin Li, Zhiyao Wang, Mingyue Liu, Xiaojuan Zhu, Baiqu Huang, Jun Lu, Zhanjun Li, Yu Zhang
Summary: This study identified the upregulation of miR-59 in HGPS patient cells and HGPS mouse model, which disrupted the interaction between RNAPII and TFIIH and led to abnormal expression of cell cycle genes by targeting HMGA1 and HMGA2. Inhibition of miR-59 alleviated the cellular senescence phenotype of HGPS cells and treatment with AAV9-mediated anti-miR-59 showed therapeutic effects in the HGPS mouse model.
Review
Genetics & Heredity
Sohail Malik, Robert G. Roeder
Summary: In this Review, the authors discuss recent advances in understanding the structure and function of the Mediator and TFIID coactivators associated with the RNA polymerase II pre-initiation complex (PIC). They also explore the interaction of Mediator and TFIID with activators and their impact on PIC formation and function. The authors highlight the importance of these coactivators in determining the temporal and spatial expression patterns of genes.
NATURE REVIEWS GENETICS
(2023)
Article
Biochemistry & Molecular Biology
Pietro Berico, Max Cigrang, Guillaume Davidson, Cathy Braun, Jeremy Sandoz, Stephanie Legras, Bujamin Hektor Vokshi, Nevena Slovic, Francois Peyresaubes, Carlos Mario Gene Robles, Jean-Marc Egly, Emmanuel Compe, Irwin Davidson, Frederic Coin
Summary: The chronic inhibition of CDK7 drives melanoma cells to switch from differentiated melanocytic-type to undifferentiated mesenchymal-like cells, leading to tolerance to targeted therapies. Additionally, a GATA6-dependent gene expression program is activated, contributing to melanoma survival and targeted drug tolerance. These findings highlight the importance of CDK7 in regulating the expression of key transcription factors and genes involved in melanoma progression and resistance to treatment.
Editorial Material
Biochemistry & Molecular Biology
Allison C. Schier, Dylan J. Taatjes
Summary: After years of low-resolution and partial assemblies, recent papers have provided a clearer understanding of transcription initiation by RNA polymerase II, including the structure of the entire human preinitiation complex.
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Eric J. Tomko, Olivia Luyties, Jenna K. Rimel, Chi-Lin Tsai, Jill O. Fuss, James Fishburn, Steven Hahn, Susan E. Tsutakawa, Dylan J. Taatjes, Eric A. Galburt
Summary: The general transcription factor TFIIH contains three ATP-dependent catalytic activities and functions in nucleotide excision repair and Pol II transcription initiation. While the functions are conserved between metazoans and yeast, yeast TFIIH drives transcription start-site scanning. Human and yeast core-TFIIH complexes lack processive translocation, with the yeast kinase module aiding in robust transcription start-site scanning.
JOURNAL OF MOLECULAR BIOLOGY
(2021)
Article
Oncology
John Gallon, Antonio Rodriguez-Calero, Andrej Benjak, Dilara Akhoundova, Sina Maletti, Ursula Amstutz, Ekkehard Hewer, Vera Genitsch, Achim Fleischmann, Elisabeth J. Rushing, Rainer Grobholz, Ingeborg Fischer, Wolfram Jochum, Gieri Cathomas, Adeboye O. Osunkoya, Lukas Bubendorf, Holger Moch, George Thalmann, Felix Y. Feng, Silke Gillessen, Charlotte K. Y. Ng, Mark A. Rubin, Salvatore Piscuoglio
Summary: Metastases from primary prostate cancers to rare locations, such as the brain, are becoming more common due to longer life expectancy. Epigenetic dysregulation and distinct DNA methylation profiles are associated with primary prostate cancer and prostate cancer brain metastases (PCBM). This study analyzed the DNA methylation landscapes of PCBM, identified associations with mutational background and PRC2 complex activity, and discovered specific epigenetic alterations potentially involved in PCBM formation.
Article
Medicine, Research & Experimental
Lila Rouland, Eric Duplan, Ligia Ramos dos Santos, Aurore Bernardin, Karen S. Katula, Guidalberto Manfioletti, Ahmed Idbaih, Frederic Checler, Cristine Alves da Costa
Summary: The study demonstrates the tumor suppressor function of Parkin in controlling GBM cell proliferation, with Cyclin A regulated by PK's transcription factor function and Cyclin B by both E3-ligase and transcription factor functions. Invalidation of PK leads to enhanced tumor progression in immunocompetent mice, suggesting an impact of PK-dependent tumor environment. Parkin is secreted by neuronal cells and recaptured by tumor cells, lowering Cyclin levels and decreasing GBM cell proliferation. Additionally, PK expression is decreased in human GBM biopsies and inversely correlated to Cyclin A and Cyclin B expressions.
Article
Multidisciplinary Sciences
Cristina Ribeiro-Silva, Mariangela Sabatella, Angela Helfricht, Jurgen A. Marteijn, Arjan F. Theil, Wim Vermeulen, Hannes Lans
NATURE COMMUNICATIONS
(2020)
Article
Cell Biology
Mariangela Sabatella, Karen L. Thijssen, Carlota Davo-Martinez, Wim Vermeulen, Hannes Lans
Summary: Research has shown that there are tissue-specific differences in DNA repair activity, with muscle cells appearing to be more resistant to the effects of DNA damage compared to neurons.
Article
Cell Biology
Ying Zhang, Imke K. Mandemaker, Syota Matsumoto, Oded Foreman, Christopher P. Holland, Whitney R. Lloyd, Kaoru Sugasawa, Wim Vermeulen, Jurgen A. Marteijn, Paul J. Galardy
Summary: Nucleotide excision repair pathway is essential for fixing DNA damage, and the UV-DDB complex plays a key role in recognizing and repairing UV-induced lesions. The tumor suppressor USP44 deubiquitinates DDB2 to prevent premature degradation, ensuring proper recruitment of repair components. Lack of USP44 leads to impaired repair and increases susceptibility to NER-induced tumors.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Cell Biology
Marit E. Geijer, Di Zhou, Kathiresan Selvam, Barbara Steurer, Chirantani Mukherjee, Bastiaan Evers, Simona Cugusi, Marvin van Toorn, Melanie van der Woude, Roel C. Janssens, Yannick P. Kok, Wenzhi Gong, Anja Raams, Calvin S. Y. Lo, Joyce H. G. Lebbink, Bart Geverts, Dalton A. Plummer, Karel Bezstarosti, Arjan F. Theil, Richard Mitter, Adriaan B. Houtsmuller, Wim Vermeulen, Jeroen A. A. Demmers, Shisheng Li, Marcel A. T. M. van Vugt, Hannes Lans, Rene Bernards, Jesper Q. Svejstrup, Arnab Ray Chaudhuri, John J. Wyrick, Jurgen A. Marteijn
Summary: Correct transcription is crucial for life, and cells have intricate mechanisms to counteract transcription-blocking lesions. The elongation factor ELOF1 plays an important role in the transcription stress response following DNA damage, protecting the transcription machinery via two distinct mechanisms.
NATURE CELL BIOLOGY
(2021)
Article
Biology
Karen L. Thijssen, Melanie van der Woude, Carlota Davo-Martinez, Dick H. W. Dekkers, Mariangela Sabatella, Jeroen A. A. Demmers, Wim Vermeulen, Hannes Lans
Summary: The TFIIH complex is essential for transcription and nucleotide excision repair, with mutations in its smallest subunit TTDA/GTF2H5 leading to trichothiodystrophy. While TTDA/GTF2H5 knockout mice are not viable, a C. elegans model shows GTF-2H5 deficiency is compatible with life and can be used for studying the disease's pathogenesis.
COMMUNICATIONS BIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Alba Muniesa-Vargas, Arjan F. Theil, Cristina Ribeiro-Silva, Wim Vermeulen, Hannes Lans
Summary: The XPG/ERCC5 endonuclease is the causative gene for Xeroderma Pigmentosum complementation group G. It plays a critical role in removing DNA damage in nucleotide excision repair and has additional important functions in genome maintenance, such as protecting replication forks and resolving R-loops. XPG deficiency is associated with various disease phenotypes.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Marvin van Toorn, Yasemin Turkyilmaz, Sueji Han, Di Zhou, Hyun-Suk Kim, Irene Salas-Armenteros, Mihyun Kim, Masaki Akita, Franziska Wienholz, Anja Raams, Eunjin Ryu, Sukhyun Kang, Arjan F. Theil, Karel Bezstarosti, Maria Tresini, Giuseppina Giglia-Mari, Jeroen A. Demmers, Orlando D. Scha, Jun-Hyuk Choi, Wim Vermeulen, Jurgen A. Marteijn
Summary: Nucleotide excision repair (NER) is a mechanism that removes DNA damage through a cut-and-patch reaction, which helps prevent cancer and aging. HLTF is an important factor in NER that actively evicts DNA damage to coordinate the transition between excision and DNA synthesis steps, thereby safeguarding genome integrity.
Article
Multidisciplinary Sciences
Florent Taupelet, Lise-Marie Donnio, Charlene Magnani, Pierre-Olivier Mari, Giuseppina Giglia-Mari
Summary: Nucleotide Excision Repair is a DNA repair system involving multiple proteins. Mutations in genes coding for these proteins can cause rare diseases such as Xeroderma Pigmentosum and Cockayne Syndrome. Our study found that XPG deficiency affects ribosome biogenesis and neuronal development, possibly through increased binding of UBF and unresolved R-loops along the ribosomal DNA gene.
Article
Biology
Lise-Marie Donnio, Elena Cerutti, Charlene Magnani, Damien Neuillet, Pierre-Olivier Mari, Giuseppina Giglia-Mari
Summary: XAB2 is a multifunctional protein involved specifically in the transcription-coupled nucleotide excision repair (TC-NER) reactions for RNA polymerase 2-transcribed genes. Unlike other NER proteins, XAB2 does not accumulate on local UV damage and becomes more mobile after damage induction. This study also reveals that XAB2 is released from DNA:RNA hybrids and the CSA and XPG proteins after DNA damage induction, contributing to the DNA damage recognition step during TC-NER.
Article
Biochemistry & Molecular Biology
Carlota Davo-Martinez, Angela Helfricht, Cristina Ribeiro-Silva, Anja Raams, Maria Tresini, Sidrit Uruci, Wiggert A. van Cappellen, Nitika Taneja, Jeroen A. A. Demmers, Alex Pines, Arjan F. Theil, Wim Vermeulen, Hannes Lans
Summary: The SWI/SNF family of ATP-dependent chromatin remodeling complexes is frequently mutated in cancer and is involved in multiple DNA damage response mechanisms. Different subunits of the BAF, PBAF and ncBAF complexes are recruited to double-strand breaks (DSBs) in a transcription-dependent manner and promote homologous recombination. PBAF and ncBAF complexes facilitate RNA polymerase II eviction and initiate transcriptional silencing near DNA damage, while BAF complex helps to maintain this silencing. ARID1A-containing BAF complexes aid in R-loop resolution and DNA repair by promoting the recruitment of RNaseH1 and RAD52.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Elena Botta, Arjan F. Theil, Anja Raams, Giuseppina Caligiuri, Sarah Giachetti, Silvia Bione, Maria Accadia, Anita Lombardi, Desiree E. C. Smith, Marisa Mendes, Sigrid M. A. Swagemakers, Peter J. Van der Spek, Gajja S. Salomons, Jan H. J. Hoeijmakers, Dhanya Yesodharan, Sheela Nampoothiri, Tomoo Ogi, Alan R. Lehmann, Donata Orioli, Wim Vermeulen
Summary: Trichothiodystrophy (TTD) is a rare hereditary neurodevelopmental disorder characterized by sulfur-deficient brittle hair, nails, and scaly skin, with highly variable clinical features. New gene defects have been identified to cause the non-photosensitive forms of TTD (NPS-TTD), impacting the stability of tRNA synthetases and protein translation. This study redefines TTD as a syndrome where proteins involved in gene expression are unstable, affecting both translation and transcription.
HUMAN MOLECULAR GENETICS
(2021)
