Article
Biotechnology & Applied Microbiology
Martina Fiumara, Samuele Ferrari, Attya Omer-Javed, Stefano Beretta, Luisa Albano, Daniele Canarutto, Angelica Varesi, Chiara Gaddoni, Chiara Brombin, Federica Cugnata, Erika Zonari, Matteo Maria Naldini, Matteo Barcella, Bernhard Gentner, Ivan Merelli, Luigi Naldini
Summary: Base and prime editors have shown potential for precise genetic engineering, but their cellular responses and genotoxicity are not well understood. This study compared the efficiency, toxicity, and genotoxicity between base and prime editors and Cas9 in human hematopoietic cells. The findings suggest that these editors can induce harmful effects and genotoxicity, raising concerns for their clinical applications.
NATURE BIOTECHNOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Jiahui Zhu, Lexin Liu, Xiaodi Ma, Xinyu Cao, Yu Chen, Xiangping Qu, Ming Ji, Huijun Liu, Chi Liu, Xiaoqun Qin, Yang Xiang
Summary: The mortality rate of idiopathic pulmonary fibrosis (IPF) increases yearly due to ineffective treatment. Oxidative stress, especially DNA stimulation, plays a crucial role in pulmonary fibrosis. DNA damage is important in the initiation of IPF and DNA repair systems targeting damage are crucial for lung cell survival. However, existing research has not focused on the role of DNA damage and repair pathways in IPF.
Review
Biochemistry & Molecular Biology
Inga R. Grin, Daria V. Petrova, Anton V. Endutkin, Chunquan Ma, Bing Yu, Haiying Li, Dmitry O. Zharkov
Summary: Base excision DNA repair is an important pathway in safeguarding the genome of plants, and understanding their repair mechanisms is crucial for developing new crop varieties.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Microbiology
Almaz Nigatu Tesfahun, Marina Alexeeva, Migle Tomkuviene, Aysha Arshad, Prashanna Guragain, Arne Klungland, Saulius Klimasauskas, Peter Ruoff, Svein Bjelland
Summary: Mis-insertion by DNA polymerase III can lead to all possible non-cognate base pairs in DNA, resulting in base substitutions if not corrected by exonuclease or mismatch repair. In vitro evidence suggests that the C.C mismatch can be processed by base excision repair initiated by E. coli formamidopyrimidine-DNA glycosylase (Fpg). Fpg may play a role in resolving C.C and other pyrimidine.pyrimidine mismatches, increasing survival at the expense of some mutagenesis.
FRONTIERS IN MICROBIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Polina Zhdanova, Alexander A. Ishchenko, Alexander A. Chernonosov, Dmitry O. Zharkov, Vladimir V. Koval
Summary: The study reveals the structural and dynamic features of human endonuclease VIII-like protein 2 (hNEIL2), showing its unique specificity for non-canonical DNA substrates and conformational flexibility in solution.
JOURNAL OF MOLECULAR BIOLOGY
(2022)
Article
Plant Sciences
Jose Roberto Torres, Ignacio Lescano Lopez, Ana Maria Ayala, Maria Elena Alvarez
Summary: DNA glycosylases, such as MBD4L in plants, are responsible for removing mispaired or modified bases from DNA through the base excision repair (BER) pathway. This study investigates the role of Arabidopsis MBD4L in removing certain substrates from the nuclear genome in coordination with uracil DNA glycosylase (AtUNG). The findings suggest that MBD4L is critical for maintaining nuclear genome integrity and preventing cell death under genotoxic stress conditions.
Article
Microbiology
Filipe Rollo, Guilherme D. Martins, Andre G. Gouveia, Solenne Ithurbide, Pascale Servant, Celia V. Romao, Elin Moe
Summary: This study demonstrates the importance of three Endonuclease III-like enzymes encoded by genes in Deinococcus radiodurans. While DrEndoIII2 is the main enzyme in this bacterium, DrEndoIII1 and 3 show unusual and undetectable activity, respectively. The knockout mutants of these genes were more resistant to oxidative stress induced by methyl viologen, indicating the crucial role of all three EndoIII homologs for cell survival. The upregulation of EndoIII homologs gene expression in response to oxidative stress may compensate for the loss of one gene.
FRONTIERS IN MICROBIOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Yong Woong Jun, Eddy Albarran, David L. Wilson, Jun Ding, Eric T. Kool
Summary: Mitochondrial function declines with aging and neurodegeneration, largely due to accumulated mutations in mtDNA from deficient DNA repair. A fluorescent probe, UBER, was used to visualize mitochondrial BER activity, showing increased repair under oxidative stress and time delay between stress onset and BER initiation. Cells lacking MTH1 exhibited elevated demand for BER activity during extended stress, while absence of OGG1 limited glycosylation capacity.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Review
Cell Biology
Mansour Akbari, Hilde Loge Nilsen, Nicola Pietro Montaldo
Summary: Mitochondria are essential for cellular energy production and play a crucial role in organismal development and normal function. Understanding the mechanisms of mtDNA maintenance and transcription can provide insights into the pathogenesis of various diseases.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Review
Biology
Susan S. Wallace
Summary: The research in the laboratory over 50 years focused on DNA enzymes and radiation damage repair, specifically identifying and characterizing DNA glycosylases. This research has provided insights into the repair mechanisms of DNA damages induced by radiation.
INTERNATIONAL JOURNAL OF RADIATION BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Tania Rahim, Madison A. Levinson, Kelly E. W. Carufe, Matthew Burak, Rithy Meas, Stephen Maher, Alfred L. M. Bothwell, Naomi Gades, Joann B. Sweasy
Summary: This study found that transplantation of hematopoietic cells from POLBY265C/C mice into wild-type mice leads to the development of autoimmune disease similar to lupus.
Review
Biochemistry & Molecular Biology
Sripriya Raja, Bennett Van Houten
Summary: SMUG1 is an important enzyme involved in base excision repair, with unique structure and mechanism that play a critical role in maintaining genome stability, and loss of its activity may promote cancer development.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Toxicology
Yufei Liu, Qiuhan Hua, Meizhen Li, Xueqi Li, Wei Chen, Huixian Zeng, Qinqin Diao, Changhong Shi, Yihui Ling, Yiguo Jiang
Summary: This study found that circular RNA circNIPBL promotes the DNA damage and cellular dysfunction induced by the tobacco carcinogen NNK through the base excision repair pathway. This finding further enhances our understanding of environmental carcinogenesis.
ARCHIVES OF TOXICOLOGY
(2022)
Article
Multidisciplinary Sciences
Binhan Yu, Channing C. Pletka, B. Montgomery Pettitt, Junji Iwahara
Summary: The study presents a novel NMR-based method for validating electrostatic potentials around biomolecules, demonstrating good agreement with predictions from the Poisson-Boltzmann theory. However, certain weaknesses of the theory were also illuminated, such as discrepancies in the dependence on ionic strength and potential errors due to conformational flexibility or structural uncertainties. This NMR-based method has the potential to facilitate improvements in computational approaches for electrostatic potentials.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biochemistry & Molecular Biology
Muneera Waheed Alfarhan, Heba Al-Hussaini, Narayana Kilarkaje
Summary: Type 2 diabetes negatively affects testicular structure and function, increasing oxidative DNA damage and BER protein levels. PPAR-γ modulation has minimal impact on testicular structural changes, but affects oxidative DNA damage and BER proteins.
CHEMICO-BIOLOGICAL INTERACTIONS
(2022)
Article
Chemistry, Multidisciplinary
Olayinka O. Ajani, King T. Iyaye, Damilola V. Aderohunmu, Ifedolapo O. Olanrewaju, Markus W. Germann, Shade J. Olorunshola, Babatunde L. Bello
ARABIAN JOURNAL OF CHEMISTRY
(2020)
Review
Neurosciences
Christopher N. Johnson
JOURNAL OF PHYSIOLOGY-LONDON
(2020)
Article
Chemistry, Medicinal
Zachary E. Ferris, Qiushi Li, Markus W. Germann
NATURAL PRODUCT COMMUNICATIONS
(2019)
Article
Cell Biology
Christopher N. Johnson, Rekha Pattanayek, Franck Potet, Robyn T. Rebbeck, Daniel J. Blackwell, Roman Nikolaienko, Vasco Sequeira, Remy Le Meur, Przemyslaw B. Radwanski, Jonathan P. Davis, Aleksey Zima, Razvan L. Cornea, Steven M. Damo, Sandor Gyorke, Alfred L. George, Bjorn C. Knollmann
Article
Biochemical Research Methods
Eric A. Owens, Hang T. Huynh, Ekaterina M. Stroeva, Arghya Barman, Kostiantyn Ziabrev, Ananya Paul, Sarah V. Nguyen, Matthew Laramie, Donald Hamelberg, Markus W. Germann, W. David Wilson, Maged Henary
BIOCONJUGATE CHEMISTRY
(2019)
Article
Cardiac & Cardiovascular Systems
Lisa M. Wren, Juan Jimenez-Jaimez, Saleh Al-Ghamdi, Jumana Y. Al-Aama, Amnah Bdeir, Zuhair N. Al-Hassnan, Jyn L. Kuan, Roger Y. Foo, Franck Potet, Christopher N. Johnson, Miriam C. Aziz, Gemma L. Carvill, Juan-Pablo Kaski, Lia Crotti, Francesca Perin, Lorenzo Monserrat, Paul W. Burridge, Peter J. Schwartz, Walter J. Chazin, Zahurul A. Bhuiyan, Alfred L. George
CIRCULATION-GENOMIC AND PRECISION MEDICINE
(2019)
Review
Biochemistry & Molecular Biology
Walter J. Chazin, Christopher N. Johnson
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2020)
Article
Medicine, Research & Experimental
Josine M. de Winter, Joery P. Molenaar, Michaela Yuen, Robbert van der Pijl, Shengyi Shen, Stefan Conijn, Martijn van de Locht, Menne Willigenburg, Sylvia J. P. Bogaards, Esmee S. B. van Kleef, Saskia Lassche, Malin Persson, Dilson E. Rassier, Tamar E. Sztal, Avnika A. Ruparelia, Viola Oorschot, Georg Ramm, Thomas E. Hall, Zherui Xiong, Christopher N. Johnson, Frank Li, Balazs Kiss, Noelia Lozano-Vidal, Reinier A. Boon, Manuela Marabita, Leonardo Nogara, Bert Blaauw, Richard J. Rodenburg, Benno Kusters, Jonne Doorduin, Alan H. Beggs, Henk Granzier, Ken Campbell, Weikang Ma, Thomas Irving, Edoardo Malfatti, Norma B. Romero, Robert J. Bryson-Richardson, Baziel G. M. van Engelen, Nicol C. Voermans, Coen A. C. Ottenheijm
JOURNAL OF CLINICAL INVESTIGATION
(2020)
Article
Multidisciplinary Sciences
Suela Xhani, Sangchoon Lee, Hye Mi Kim, Siming Wang, Shingo Esaki, Van L. T. Ha, Mahtab Khanezarrin, Giselle L. Fernandez, Amanda Albrecht, James M. Aramini, Markus W. Germann, Gregory M. K. Poon
Article
Multidisciplinary Sciences
D. Julia Trembinski, Diewertje I. Bink, Kosta Theodorou, Janina Sommer, Ariane Fischer, Anke van Bergen, Chao-Chung Kuo, Ivan G. Costa, Christoph Schuermann, Matthias S. Leisegang, Ralf P. Brandes, Tijna Alekseeva, Boris Brill, Astrid Wietelmann, Christopher N. Johnson, Alexander Spring-Connell, Manuel Kaulich, Stanislas Werfel, Stefan Engelhardt, Marc N. Hirt, Kaja Yorgan, Thomas Eschenhagen, Luisa Kirchhof, Patrick Hofmann, Nicolas Jae, Ilka Wittig, Nazha Hamdani, Corinne Bischof, Jaya Krishnan, Riekelt H. Houtkooper, Stefanie Dimmeler, Reinier A. Boon
NATURE COMMUNICATIONS
(2020)
Article
Biochemistry & Molecular Biology
Archana Iyer, Renata A. G. Reis, Swathi Gannavaram, Mohamed Momin, Alexander M. Spring-Connell, Yoelvis Orozco-Gonzalez, Johnson Agniswamy, Donald Hamelberg, Irene T. Weber, Samer Gozem, Siming Wang, Markus W. Germann, Giovanni Gadda
Summary: This study demonstrated how an active site residue changes enzyme reactivity by modulating fluctuations between conformational states, resulting in an enzyme with different activities. The replacement of tyrosine 249 with phenylalanine in the active site yielded an enzyme variant with both active and inactive FAD, showing no structural differences compared to the wild-type enzyme. Molecular dynamics simulations revealed an alternate conformation in the variant enzyme that samples a metastable state and has differences in flavin electronics compared to the wild type.
Review
Biochemistry & Molecular Biology
Ryan B. Williams, Christopher N. Johnson
Summary: Calcineurin, also known as protein phosphatase 2B, is a crucial serine threonine phosphatase involved in multiple signaling pathways. Despite extensive research on its role in cardiac disease, clarification is needed on its physiological function in healthy cardiomyocytes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Chemistry, Medicinal
Bin Sun, Xuan Fang, Christopher N. Johnson, Garrett Hauck, Yongjun Kou, Jonathan P. Davis, Peter M. Kekenes-Huskey
Summary: Plant-derived CaM variants sCaM-1 and sCaM-4 exhibit similar Ca2+ and canonical CaMBR binding properties as mammalian CaM (mCaM), but show weakened binding with a secondary region in CaN, suggesting a mechanism for differential regulation of CaN activity that involves interactions beyond traditional Ca2+ and CaMBR binding.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2021)
Editorial Material
Physiology
Robert Szulcek, Christopher N. Johnson, James Todd Pearson, Vasco Sequeira
FRONTIERS IN PHYSIOLOGY
(2022)
Article
Cell Biology
Ryan B. Williams, Md Nure Alam Afsar, Svetlana Tikunova, Yongjun Kou, Xuan Fang, Radha P. Somarathne, Rita F. Gyawu, Garrett M. Knotts, Taylor A. Agee, Sara A. Garcia, Luke D. Losordo, Nicholas C. Fitzkee, Peter M. Kekenes-Huskey, Jonathan P. Davis, Christopher N. Johnson
Summary: Calmodulin (CaM) is a calcium-sensing protein that regulates various processes in the body. Mutations in CaM can lead to life-threatening heart disease. This study investigates how disease-associated CaM mutations affect the activity of the phosphatase protein CaN and suggests a potential contribution of altered CaN function to calmodulinopathy.