Article
Chemistry, Multidisciplinary
Alex Gibney, Raphael E. F. de Paiva, Vandana Singh, Robert Fox, Damien Thompson, Joseph Hennessy, Creina Slator, Christine J. McKenzie, Pegah Johansson, Vickie McKee, Fredrik Westerlund, Andrew Kellett
Summary: In this study, a Cu-catalysed azide-alkyne cycloaddition reaction produced a 1,2,3-triazole linker that was used to create Cu-binding artificial metallo-nucleases (AMNs). A bioactive C-3-symmetric ligand called TC-Thio was developed using biologically inert reaction partners. The ligand formed Cu-II and Cu-I complexes through Cu coordination, and showed potent DNA binding and cleaving abilities. Mechanistic studies revealed that DNA recognition occurred at the minor groove, leading to oxidative damage through a pathway dependent on superoxide and peroxide. Single molecule imaging demonstrated that the complex caused DNA damage recognized by base excision repair enzymes, comparable to the clinical drug temozolomide.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Biochemistry & Molecular Biology
Barbara de la Pena Avalos, Nicolas Paquet, Romain Tropee, Yan Coulombe, Hannah Palacios, Justin W. Leung, Jean-Yves Masson, Pascal H. G. Duijf, Eloise Dray
Summary: Efficient DNA repair and limitation of genome rearrangements depend on the crosstalk between different DNA double-strand break (DSB) repair pathways and their synchronization with the cell cycle. This study identifies EYA4 as a protein phosphatase that dephosphorylates RAD51, a key player in homologous recombination (HR) at DSBs. EYA4 regulates RAD51 localization, filament formation, foci formation, and activity through its tyrosine phosphatase activity. The findings have implications for understanding the pathological version of RAD51 in EYA4-overexpressing cancers.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Multidisciplinary Sciences
Jiangbin Wei, Qiwu Shi, Lidan Xiong, Guang Xin, Tao Yi, Yunqing Xiao, Wanxia Huang
Summary: The study investigated the biological effects of radiation from the SG-III prototype laser facility on HaCat cells and PC12 cells, finding that the damage to cells was dose-dependent and induced DNA damage and apoptotic necrosis. Transcriptome and protein analysis revealed pathways involving proliferation, transformation, necrosis, inflammation response, apoptosis, and DNA damage repair were activated, suggesting potential harm to biological safety.
SCIENTIFIC REPORTS
(2021)
Article
Multidisciplinary Sciences
Amy Wilson, Piotr Grabowski, Joanne Elloway, Stephanie Ling, Jonathan Stott, Ann Doherty
Summary: An automated, high-content, high throughput, image-based in vitro Micronucleus assay has been developed and validated to provide a comprehensive analysis of small molecule genotoxic potential. By utilizing computational approaches and machine learning models, different types of genotoxic compounds within the data set can be accurately identified, reducing analysis time and minimizing human bias.
SCIENTIFIC REPORTS
(2021)
Article
Medicine, Research & Experimental
Yizhu Li, Yurong Ling, Morten O. Loehr, Sabrina Chaabane, Oh Wan Cheng, Kaifeng Zhao, Chao Wu, Moritz Buescher, Jana Weber, Daria Stomakhine, Marina Munker, Ronja Pientka, Sarah B. Christ, Matthias Dobbelstein, Nathan W. Luedtke
Summary: This study reports the synergistic cytotoxicity of VdU and PINK in cultured human cells by inducing DNA damage and reducing cell viability. The combination of VdU and PINK provides a novel and promising approach for cancer treatment via selective induction of DNA damage.
Article
Biology
Mark C. Johnson, Geylani Can, Miguel Monteiro Santos, Diana Alexander, Philip Zegerman
Summary: This study reveals that Rad53 phosphorylates the same substrates throughout the cell cycle, not just in S-phase, suggesting its roles beyond S-phase. By inhibiting 51d3 and Dbf4, Rad53 limits re-replication in G2/M, preventing gene amplification, and inhibiting these substrates in G1 prevents premature initiation at the G1/S transition. This redefinition of the 'S-phase checkpoint' has implications for understanding checkpoint function in cancers without proper cell cycle controls.
Article
Oncology
Amandine Moretton, Jana Slyskova, Marwan E. Simaan, Emili A. Arasa-Verge, Mathilde Meyenberg, D. Alonso Cerron-Infantes, Miriam M. Unterlass, Joanna I. Loizou
Summary: In this study, a series of cisplatin derivatives compatible with click chemistry were synthesized to investigate the repair of DNA crosslinks and cellular responses. It was found that these compounds bind to DNA and generate DNA damage. They can be visualized and quantified in cells through fluorescence probes and biotin tagging, respectively. Furthermore, one of the compounds can be used to identify DNA repair proteins.
FRONTIERS IN ONCOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Yo-Chuen Lin, Dazhen Liu, Arindam Chakraborty, Virgilia Macias, Eileen Brister, Jay Sonalkar, Linyuan Shen, Jaba Mitra, Taekjip Ha, Andre Kajdacsy-Balla, Kannanganattu V. Prasanth, Supriya G. Prasanth
Summary: The smallest subunit of the human Origin Recognition Complex, hOrc6, is necessary for DNA replication progression and is involved in mismatch repair during S-phase. The molecular mechanisms of how hOrc6 regulates DNA replication and damage response are still unclear. Elevated levels of Orc6 and reduced phosphorylation at Thr229 are observed in colorectal cancers, and this may lead to uncontrolled cell proliferation. Based on these findings, DNA-damage-induced hOrc6-pThr229 phosphorylation during S-phase may facilitate ATR signaling, halt fork progression, and promote efficient repair to prevent tumorigenesis.
MOLECULAR AND CELLULAR BIOLOGY
(2023)
Article
Oncology
Ayuna Hattori, Emi Takamatsu-Ichihara, Yoshiki Yamamoto, Shuhei Fujita, Kazutsune Yamagata, Takuo Katsumoto, Yukino Machida, Haruka Shinohara, Ryo Murakami, Issay Kitabayashi
Summary: The chromatin-associated AAA+ ATPases Tip48 and Tip49 are crucial for various nuclear events and frequently overexpressed in human cancers. Loss of Tip49 triggers p53-dependent apoptosis and inhibits leukemia development. The compound DS-4950, which inhibits the ATPase activity of Tip48/49, effectively reduces tumor burden and improves survival in leukemia models. These findings suggest that Tip48/49 ATPases are functionally necessary and therapeutically targetable for the treatment of human cancers.
Article
Biochemistry & Molecular Biology
Lingyu Qiu, Wenchao Xu, Xiaopeng Lu, Feng Chen, Yongcan Chen, Yuan Tian, Qian Zhu, Xiangyu Liu, Yongqing Wang, Xin-Hai Pei, Xingzhi Xu, Jun Zhang, Wei-Guo Zhu
Summary: HDAC6 regulates DNA damage signaling by controlling the mismatch repair and nucleotide excision repair pathways. It negatively regulates DNA double-strand break (DSB) repair in an enzyme activity-independent manner. HDAC6 interacts with H2A/H2A.X to prevent its interaction with the E3 ligase RNF168, and DSBs lead to the degradation of HDAC6 and the restoration of the interaction between RNF168 and H2A/H2A.X, facilitating the recruitment of DSB repair factors to chromatin and subsequent DNA repair.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Chemistry, Multidisciplinary
Qianqian Qi, Yutong Zhang, Wei Xiong, Xingyu Liu, Shuangyu Cui, Xiaofang Ye, Kaisong Zhang, Tian Tian, Xiang Zhou
Summary: In this study, the norbornene-tetrazine ligation chemistry is used to develop clickable RNA switches in biological contexts, and its potential applications are explored. The application of RNA-based norbornene-tetrazine ligation chemistry in controlling CRISPR systems and manipulating gene editing in human cells is successfully demonstrated.
Article
Biochemistry & Molecular Biology
Linke Tang, Weifeng Yuan, Shitao Li, Xiuyan Ding, Liqian Zhu
Summary: In this study, the interaction between UV-primed global DDR and BoHV-1 productive infection was demonstrated. UV-primed global DDR differentially modulated the transcription of virus genes and stabilization of virus protein. Vice versa, the virus infection may affect UV-primed DDR signaling.
Article
Biochemistry & Molecular Biology
Maria Joao Bessa, Fatima Brandao, Paul H. B. Fokkens, Daan L. A. C. Leseman, A. John F. Boere, Flemming R. Cassee, Apostolos Salmatonidis, Mar Viana, Eliseo Monfort, Sonia Fraga, Joao Paulo Teixeira
Summary: This study assessed the toxicity of particles emitted from atmospheric plasma and high-velocity oxy-fuel thermal spraying, and found that they exerted different cytotoxic and genotoxic effects on human alveolar cells. The results emphasize the importance of considering the health risks of these process-generated particles in industrial settings.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Multidisciplinary
Xiyuan Yao, Ulrich Bierbach
Summary: A new assay method using click chemistry-enabled derivative was developed to study DNA damage caused by platinum-acridine anticancer agent in cancer cells. Results showed formation of adducts in specific gene sequences, providing insight into the pharmacological target of these agents.
CHEMISTRY-A EUROPEAN JOURNAL
(2021)
Article
Multidisciplinary Sciences
Tiberiu S. Mihaila, Carina Bate, Lynn M. Ostersehlt, Jasmin K. Pape, Jan Keller-Findeisen, Steffen J. Sahl, Stefan W. Hell
Summary: With the recent advancements in fluorescence nanoscopes, the ability to dissect nanoscopic biological structures is limited by the size of protein labels. Bioorthogonal chemical groups provide a powerful tool for specific detection of biomolecules. In this study, we introduced an engineered aminoacyl-tRNA synthetase/tRNA pair to allow for the site-specific introduction of amino acids with clickable side chains into proteins. This enhanced genetic code expansion machinery was then used to label beta-actin in cells for high-resolution imaging. Our findings highlight the need for further improvements in labeling methods to fully exploit the potential of molecular-scale optical three-dimensional resolution.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biochemistry & Molecular Biology
H. Dorota Halicka, Jorge Garcia, Jiangwei Li, Hong Zhao, Zbigniew Darzynkiewicz
Article
Cell Biology
Malgorzata Bzowska, Anna Nogiec, Krystian Bania, Magdalena Zygmunt, Miroslaw Zarebski, Jerzy Dobrucki, Krzysztof Guzik
JOURNAL OF LEUKOCYTE BIOLOGY
(2017)
Article
Biochemistry & Molecular Biology
Aleksander Szczurek, Ludger Klewes, Jun Xing, Amine Gourram, Udo Birk, Hans Knecht, Jurek W. Dobrucki, Sabine Mai, Christoph Cremer
NUCLEIC ACIDS RESEARCH
(2017)
Article
Cell Biology
Jurek Dobrucki, Noriko Saitoh
Article
Biochemistry & Molecular Biology
Marek Orlowski, Katarzyna Poplawska, Joanna Pieprzyk, Aleksandra Szczygiel-Sommer, Anna Wiech, Miroslaw Zarebski, Aneta Tarczewska, Jurek Dobrucki, Andrzej Ozyhar
BIOLOGICAL CHEMISTRY
(2018)
Review
Cell Biology
Aleksander Szczurek, Udo Birk, Hans Knecht, Jurek Dobrucki, Sabine Mai, Christoph Cremer
Review
Cell Biology
Aleksander Szczurek, Udo Birk, Hans Knecht, Jurek Dobrucki, Sabine Mai, Christoph Cremer
Article
Biochemistry & Molecular Biology
Magdalena M. Kordon, Aleksander Szczurek, Krzysztof Berniak, Oskar Szelest, Kamil Solarczyk, Magdalena Tworzydlo, Sebastian Wachsmann-Hogiu, Anne Vaahtokari, Christoph Cremer, Thoru Pederson, Jurek W. Dobrucki
Article
Multidisciplinary Sciences
Aleksander Szczurek, Fabio Contu, Agnieszka Hoang, Jurek Dobrucki, Sabine Mai
SCIENTIFIC REPORTS
(2018)
Article
Chemistry, Multidisciplinary
Miroslawa Rozycka, Ismael Coronado, Katarzyna Brach, Joanna Olesiak-Banska, Marek Samoc, Miroslaw Zarebski, Jerzy Dobrucki, Maciej Ptak, Eva Weber, Iryna Polishchuk, Boaz Pokroy, Jaroslaw Stolarski, Andrzej Ozyhar
CHEMISTRY-A EUROPEAN JOURNAL
(2019)
Article
Biochemistry & Molecular Biology
Magdalena M. Kordon, Miroslaw Zarebski, Kamil Solarczyk, Hanhui Ma, Thoru Pederson, Jurek W. Dobrucki
NUCLEIC ACIDS RESEARCH
(2020)
Review
Cell Biology
Izabela Figiel, Patrycja K. Kruk, Monika Zareba-Koziol, Paulina Rybak, Monika Bijata, Jakub Wlodarczyk, Joanna Dzwonek
Summary: The extracellular matrix plays a critical role in synaptic function, with MMP-9 and Rho GTPases identified as key factors in regulating synaptic plasticity. MMP-9 contributes to dynamic remodeling by cleaving ECM components, while Rho GTPases control cellular processes in brain physiology and pathology.
Article
Biochemistry & Molecular Biology
Aneta Tarczewska, Marta Kolonko-Adamska, Miroslaw Zarebski, Jurek Dobrucki, Andrzej Ozyhar, Beata Greb-Markiewicz
Summary: A novel purification protocol was introduced to prepare nucleocapsid protein without any bound nucleic acids, revealing significant differences in the structural properties between the contaminated and uncontaminated protein. The study suggests that nucleic acid contamination may severely affect the molecular properties of the purified nucleocapsid protein, and describes the notable ability of the protein to form condensates resembling gel-like or solid structures.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2021)
Article
Biochemistry & Molecular Biology
Magda Przybylo, Dominik Drabik, Kamila Szostak, Tomasz Borowik, Beate Klosgen, Jurek Dobrucki, Aleksander F. Sikorski, Marek Langner
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
(2017)
Article
Dermatology
J. Borowczyk-Michalowska, E. Zimolag, A. Waligorska, J. Dobrucki, Z. Madeja, J. Drukala
BRITISH JOURNAL OF DERMATOLOGY
(2017)