Article
Biochemistry & Molecular Biology
Le P. Ngo, Simran Kaushal, A. Isaac Chaim, Patrizia Mazzucato, Catherine Ricciardi, D. Leona Samson, D. Zachary Nagel, P. Bevin Engelward
Summary: By utilizing the CometChip, researchers uncovered significant variability in DNA repair efficiency among individuals, indicating its potential utility in future epidemiological and clinical studies.
FREE RADICAL BIOLOGY AND MEDICINE
(2021)
Review
Chemistry, Multidisciplinary
Jiangbo Liu, Min Li, Xiaolei Zuo
Summary: DNA nanotechnology has the potential to revolutionize live cell measurements by providing stable nanostructures for precise measurements in both intracellular and extracellular environments. Despite facing challenges, further developments in this nascent field are possible.
Article
Chemistry, Multidisciplinary
Georgina C. Gavins, Katharina Groeger, Michael D. Bartoschek, Philipp Wolf, Annette G. Beck-Sickinger, Sebastian Bultmann, Oliver Seitz
Summary: DNA nanotechnology offers opportunities for manipulating and imaging proteins on cell surfaces by creating nucleic acid-protein junctions using PNA tags. This method allows for quick assembly of different fluorescent dyes, increased brightness, reversible labeling, and is applicable to various cell and protein systems.
Article
Chemistry, Analytical
Qing-Nan Li, Dong-Xia Wang, Gui-Mei Han, Bo Liu, An-Na Tang, De-Ming Kong
Summary: The background issue in CRISPR/Cas12a-based biosensors has been efficiently solved by designing the activator strand (AS) using the RESET effect. The low background allows for sensitive detection and accurate imaging analysis of different targets in live cells, and the high-performance biosensors have potential for point-of-care testing. Several biosensing systems have been developed for the detection of nucleic acid, small molecules, and enzymes.
ANALYTICAL CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Xiangnan Wang, Xin Yi, Zhimei Huang, Jianjun He, Zhenkun Wu, Xia Chu, Jian-Hui Jiang
Summary: In this study, a repaired and activated DNAzyme (RADzyme) was developed by incorporating single methyl lesions at designated positions. This technology allowed the development of a fluorogenic RADzyme sensor for monitoring DNA repair, facilitating evaluation of repair activity in different cells and under drug treatment. This strategy provides a simple and versatile tool for the study of DNA repair biology, clinical diagnosis, and therapeutic assessment.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Biology
Thomas J. Etheridge, Desiree Villahermosa, Eduard Campillo-Funollet, Alex David Herbert, Anja Irmisch, Adam T. Watson, Hung Q. Dang, Mark A. Osborne, Antony W. Oliver, Antony M. Carr, Johanne M. Murray
Summary: The Smc5/6 complex is associated with chromatin in unchallenged cells through the non-SMC protein Nse6, involving at least two Nse6-dependent sub-pathways. Mutations in core subunits of the Smc5/6 complex affect chromatin association, with disruption of single-stranded DNA binding activity leading to elevated levels of chromosomal rearrangements during replication restart.
Article
Multidisciplinary Sciences
Alexandre Joushomme, Rosa Orlacchio, Lorenza Patrignoni, Anne Canovi, Yann Loick Chappe, Florence Poulletier De Gannes, Annabelle Hurtier, Andre Garenne, Isabelle Lagroye, Francois Moisan, Muriel Cario, Philippe Leveque, Delia Arnaud-Cormos, Yann Percherancier
Summary: The potential health risks of exposure to radiofrequency electromagnetic fields from mobile communications technologies have raised concerns. This study assessed the effects of exposure to 5G signals on molecular pathways involved in cellular stress responses. The results showed inconsistent effects in terms of cell type, SAR, exposure mode, and molecular response, indicating no conclusive evidence of molecular effects on skin cells exposed to 5G RF-EMF alone or with a chemical stressor.
SCIENTIFIC REPORTS
(2023)
Article
Chemistry, Multidisciplinary
Haw-Young Kwon, Raj Kumar Das, Gun Tae Jung, Hong-Guen Lee, Sun Hyeok Lee, Stuart N. Berry, Justin Kok Soon Tan, Solip Park, Jae-Seong Yang, Soohyun Park, Kangkyun Baek, Kyeng Min Park, Jae Won Lee, Yun-Kyu Choi, Ki Hean Kim, Sangho Kim, Kwang Pyo Kim, Nam-Young Kang, Kimoon Kim, Young-Tae Chang
Summary: The study introduces a small-molecule probe, CDgB, to differentiate B lymphocytes from T lymphocytes, which was previously only possible with the help of antibodies. It was found that B cells exhibit higher flexibility in their cell membrane and preferentially accumulate the lipid-like probe CDgB. By tracking the cell membrane changes of progenitor cells, the study revealed the dynamic reorganization of membrane properties during lymphocyte differentiation.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Genetics & Heredity
Diana A. Llerena Schiffmacher, Katarzyna W. Kliza, Arjan F. Theil, Gert-Jan Kremers, Jeroen A. A. Demmers, Tomoo Ogi, Michiel Vermeulen, Wim Vermeulen, Alex Pines
Summary: Transcription-coupled nucleotide excision repair (TC-NER) is a highly specific process that prevents cellular toxicity caused by DNA damage and maintains proper transcription. This study used a knock-in cell line to investigate the molecular dynamics of the TC-NER protein CSB in response to physiologically relevant UV doses. The researchers discovered the tightly regulated association of CSB with chromatin, controlled by the CSA-containing ubiquitin-ligase CRL complex (CRL4CSA), and identified novel CSB interactors and variations in complex composition during TC-NER progression.
Article
Microbiology
Veronica Di Antonio, Giorgio Palu, Gualtiero Alvisi
Summary: The replication of HCMV genome involves a complex interaction between host and viral products, with ppUL44 playing a crucial role in viral replication by forming protein complexes in the nucleus and cytoplasm. Our study using fluorescence and bioluminescence resonance energy transfer assays revealed the importance of ppUL44 dimerization and interaction with pUL54, providing insights for potential therapeutic targets and antiviral drug discovery.
Article
Cell Biology
Watanya Trakarnphornsombat, Hiroshi Kimura
Summary: DNA double-strand breaks (DSBs) can cause genetic mutation and histone H2AX is phosphorylated by kinases such as ATM, ATR, and DNA-PK upon DSB induction. The accumulation kinetics of ?-H2AX were similar in ATM-proficient and-deficient cells, but delayed in the presence of a DNA-PK inhibitor. Ku80 (XRCC5) diffuses freely in the nucleus, while ATM repeatedly binds to and dissociates from chromatin. ATM accumulation at damage sites is regulated by the histone acetyltransferase MOF, but does not necessarily reflect in the ?-H2AX level, suggesting distinct actions of ATM and DNA-PK in immediate ?-H2AX accumulation.
JOURNAL OF CELL SCIENCE
(2023)
Editorial Material
Oncology
Anton G. Henssen
Summary: A CRISPR-based method for imaging ecDNA in live cells, called ecTag, has been developed, revealing important features of ecDNA in cancer cells.
Article
Biochemistry & Molecular Biology
Zhihui Liu, Michael J. Kruhlak, Carol J. Thiele
Summary: Zinc finger transcription factor CASZ1b is essential for nervous system development and suppresses neuroblastoma growth. Our study investigates the recruitment of CASZ1b to sites of DNA damage, showing that CASZ1b is transiently recruited to these sites and that its recruitment is dependent on PARP and specific DNA binding motifs. Loss of CASZ1b increases cell sensitivity to DNA damage induced by gamma irradiation and suggests a role for CASZ1b in regulating DNA repair efficiency during development and tumorigenesis.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Yuko Hasegawa, Kevin Struhl
Summary: The transcription factor SP1 exhibits varying binding dynamics at different target sites in the human genome, potentially influenced by factors such as location and cobinding factors.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Chemistry, Analytical
Shiyi Xie, Benfeng Xu, Rui Tang, Siyu Chen, Chunyang Lei, Zhou Nie
Summary: In this study, the CRISPR/Cas12a system was utilized as a direct sensing system for Mn2+ detection in living cells. It was found that Mn2+ can accelerate the cleavage kinetics of Cas12a, allowing for robust detection of Mn2+ in complex biological samples and in the cytoplasm of living cells. The system was also applied to study the cytotoxicity of Mn2+ in nerve cells.
ANALYTICAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Despina Serlidaki, Maria A. W. H. van Waarde, Lukas Rohland, Anne S. Wentink, Suzanne L. Dekker, Maarten J. Kamphuis, Jeffrey M. Boertien, Jeanette F. Brunsting, Nadinath B. Nillegoda, Bernd Bukau, Matthias P. Mayer, Harm H. Kampinga, Steven Bergink
JOURNAL OF BIOLOGICAL CHEMISTRY
(2020)
Article
Multidisciplinary Sciences
Elisabeth Anne Adanma Obara, Diana Aguilar-Morante, Rikke Darling Rasmussen, Alex Frias, Kristoffer Vitting-Serup, Yi Chieh Lim, Kirstine Juul Elbaek, Henriette Pedersen, Lina Vardouli, Kamilla Ellermann Jensen, Jane Skjoth-Rasmussen, Jannick Brennum, Lucie Tuckova, Robert Strauss, Christoffel Dinant, Jiri Bartek, Petra Hamerlik
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
Shannon McMahon, Steven Bergink, Harm H. Kampinga, Heath Ecroyd
Summary: The study shows that DNAJB proteins can inhibit protein aggregation by supporting the Hsp70-dependent degradation pathway, different from the mechanism of preventing fibrillar aggregation. The research also found that DNAJB6 and DNAJB8 have two distinct regions for binding substrates.
JOURNAL OF CELL SCIENCE
(2021)
Article
Biochemistry & Molecular Biology
Gabriel Vasata Furtado, Jing Yang, Di Wu, Christos Papagiannopoulos, Hanna M. Terpstra, E. F. Elsiena Kuiper, Sybille Krauss, Wei-Guo Zhu, Harm H. Kampinga, Steven Bergink
Summary: FOXO1 prevents toxic polyQ aggregation and reduces the synthesis rate of proteins from pathogenic CAG repeat transcripts, thereby decreasing the initiation of amyloidogenesis in CAG-repeat diseases.
HUMAN MOLECULAR GENETICS
(2021)
Article
Oncology
Malene Bredahl Hansen, Maria Postol, Siri Tvingsholm, Inger Odum Nielsen, Tiina Naumanen Dietrich, Pietri Puustinen, Kenji Maeda, Christoffel Dinant, Robert Strauss, David Egan, Marja Jaattela, Tuula Kallunki
Summary: This study identified several efficient inhibitors of invasive growth in HER2 positive cancers resistant to first and second-line treatments, by targeting lysosomal pathways downstream of ErbB2. The drugs classified into different groups based on their ability to induce autophagy and/or lysosomal membrane permeabilization, providing potential targets for preventing cancer cell spreading. Additionally, these drugs possess anti-inflammatory activities, suggesting they could be used as multipurpose drugs targeting both infection/inflammation and cancer spreading simultaneously.
Review
Biochemistry & Molecular Biology
Anna Ainslie, Wouter Huiting, Lara Barazzuol, Steven Bergink
Summary: Genome instability and loss of protein homeostasis are fundamental characteristics of age-related diseases, particularly neurodegenerative diseases such as Alzheimer's, Parkinson's, Huntington's, and ALS. These events are interconnected and contribute to the development of neurological diseases.
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
Multidisciplinary Sciences
Daniel Gomez-Cabello, Giorgios Pappas, Diana Aguilar-Morante, Christoffel Dinant, Jiri Bartek
Summary: RNA plays a crucial role in DNA damage repair. This study demonstrates that the interplay of RNAPII-generated nascent RNA, RNA:DNA hybrids, and the resection factor CtIP guides the choice of DNA double-strand break repair pathway towards error-free homologous recombination.
NATURE COMMUNICATIONS
(2022)
Article
Cell Biology
Ditte L. Fogde, Cristina P. R. Xavier, Kristina Balnyte, Lya K. K. Holland, Kamilla Stahl-Meyer, Christoffel Dinant, Elisabeth Corcelle-Termeau, Cristina Pereira-Wilson, Kenji Maeda, Marja Jaattela
Summary: Ursolic acid, a naturally occurring compound, has anti-inflammatory and anti-tumor effects. This study reveals that its anti-cancer activity is achieved by targeting lysosomal function, disrupting apoptosis and autophagy pathways to kill cancer cells. Combination treatment with cationic amphiphilic drugs can enhance the anti-cancer effect of ursolic acid.
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)