Article
Genetics & Heredity
Nadejda I. Rechkunova, Polina V. Zhdanova, Natalia A. Lebedeva, Ekaterina A. Maltseva, Vladimir V. Koval, Olga I. Lavrik
Summary: DNA polymerases beta and lambda have structural and functional differences, with their positioning of the trans-BP-dG residue being a significant structural distinction that may explain their variations in gap-filling and translesion synthesis.
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)
Editorial Material
Biochemistry & Molecular Biology
Susan E. Tsutakawa, Altaf H. Sarker
Summary: The canonical role of DNA glycosylase is in repairing global base damage, but it also plays a role in epigenetic gene regulation, immune response modulation, replication, and transcription. In this issue of Structure, Eckenroth et al. (2020) reveal the structure of NEIL2 glycosylase, showing that its catalytic domain flexibility sets it apart from other glycosylases and implies novel regulatory mechanisms.
Article
Multidisciplinary Sciences
Adarsh Kumar, Andrew J. Reed, Walter J. Zahurancik, Sasha M. Daskalova, Sidney M. Hecht, Zucai Suo
Summary: Base excision repair (BER) is a crucial cellular pathway for DNA damage repair, and DNA polymerase beta (Pol beta) plays a key role in this process. This study reveals the sequential order of two enzymatic activities of Pol beta during BER and identifies the intermediate molecules involved. The coordinated activities of Pol beta's active sites are found to be critical for the BER pathway, suggesting potential alternative strategies for therapeutic intervention.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Clinical Neurology
Mehmet Utku Kucuker, Aysegul Ozerdem, Deniz Ceylan, Alejandra Cabello-Arreola, Ada M. C. Ho, Boney Joseph, Lauren M. Webb, Paul E. Croarkin, Mark A. Frye, Marin Veldic
Summary: This systematic review examined the role of DNA repair enzymes, particularly base excision repair (BER), in mood disorders. The study found that SNPs of several BER genes are associated with MDD and BD, but conflicting findings and limited studies make it difficult to draw definitive conclusions about BER gene expression. Further research comparing DNA repair during episodes of mood disorders to remission may provide valuable insights into the role of DNA repair in these conditions.
JOURNAL OF AFFECTIVE DISORDERS
(2022)
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.
Article
Agronomy
Shiwen Liu, Shuhua Zhu, Guangqin Jing
Summary: Excessive reactive oxygen species (ROS) during storage can lead to oxidative damage to mitochondrial DNA (mtDNA) in peaches, exacerbating fruit damage. Nitric oxide (NO) has been found to help maintain the storage quality of peaches. This study investigates the effects of NO on mtDNA damage and repair, focusing on the base excision repair (BER) pathway. The results show that NO reduces ROS levels and oxidative damage markers in mitochondria, increases mtDNA copy number, and enhances the BER pathway, leading to improved repair efficiency and maintenance of mtDNA integrity.
POSTHARVEST BIOLOGY AND TECHNOLOGY
(2023)
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
Biochemistry & Molecular Biology
Vladimir Shafirovich, Nicholas E. Geacintov
Summary: Base excision repair (BER) and nucleotide excision repair (NER) are two major mechanisms that remove DNA lesions. Experimental evidence shows that oxidatively generated DNA lesions can be repaired by both competitive BER and NER pathways. The interaction between BER and NER pathways in repairing oxidatively generated DNA lesions is crucial for understanding DNA repair mechanisms.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(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
Genetics & Heredity
Andrea M. Kaminski, Thomas A. Kunkel, Lars C. Pedersen, Katarzyna Bebenek
Summary: 8-oxo-guanine (8OG) is a common base lesion associated with human diseases such as cancer, aging-related neurodegenerative disorders, and atherosclerosis. It is highly mutagenic and poses challenges for DNA polymerases in replicating and repairing genomic or mitochondrial DNA correctly.
Article
Immunology
Maria Belland Olsen, Camilla Huse, Mirta Mittelstedt Leal de Sousa, Sarah Louise Murphy, Antonio Sarno, Tobias Sebastian Obermann, Kuan Yang, Jan Cato Holter, Marte Jontvedt Jorgensen, Erik Egeland Christensen, Wei Wang, Ping Ji, Lars Heggelund, Hedda Hoel, Anne Margarita Dyrhol-Riise, Ida Gregersen, Pal Aukrust, Magnar Bjoras, Bente Halvorsen, Tuva Borresdatter Dahl
Summary: This study aimed to investigate DNA damage and repair in Covid-19 patients. The results showed that patients had comparable levels of DNA damage to healthy controls, but levels of DNA repair proteins were significantly increased, indicating enhanced DNA repair during acute infection. Gene expression analysis also revealed the involvement of DNA repair genes in respiratory failure. Furthermore, the regulation of DNA repair pathway was more significant during Covid-19 compared to other viral or bacterial infections.
JOURNAL OF INFLAMMATION RESEARCH
(2022)
Review
Biochemistry & Molecular Biology
Yuliya Krasikova, Nadejda Rechkunova, Olga Lavrik
Summary: Nucleotide excision repair (NER) is a versatile DNA repair pathway that is linked to neurological degeneration in patients with Xeroderma pigmentosum. Xeroderma pigmentosum patients typically have a high sensitivity to ultraviolet light due to DNA repair defects, leading to multiple skin and eye cancers.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Filipe Rollo, Patricia T. Borges, Celia M. Silveira, Margarida T. G. Rosa, Smilja Todorovic, Elin Moe
Summary: This study investigated the structure and mechanism of the three EndoIII enzymes in Deinococcus radiodurans, revealing their different activities and specificities, which is important for addressing questions regarding their presence and characteristics in the organism.
Review
Biochemistry & Molecular Biology
Weiran Zhang, Ranwei Zhong, Xiangping Qu, Yang Xiang, Ming Ji
Summary: Excess reactive oxygen species (ROS) can lead to oxidative stress by disrupting the balance between oxidation and anti-oxidation. The main product of ROS-induced base damage is 8-hydroxyguanine (8-oxoG), which can cause mutations if not promptly removed during DNA replication. The OGG1-mediated oxidative damage repair pathway plays an important role in preventing dysfunction caused by oxidative stress.
Article
Pharmacology & Pharmacy
Laura Bavagnoli, Giulia Campanini, Maurizio Forte, Giorgia Ceccotti, Elena Percivalle, Silvia Bione, Antonella Lisa, Fausto Baldanti, Giovanni Maga
ANTIVIRAL RESEARCH
(2019)
Article
Chemistry, Medicinal
Marianna Nalli, Jorge Armijos Rivera, Domiziana Masci, Antonio Coluccia, Roger Badia, Eva Riveira-Munoz, Alessandro Brambilla, Elisabetta Cinquina, Ombretta Turriziani, Francesca Falasca, Myriam Catalano, Cristina Limatola, Jose A. Este, Giovanni Maga, Romano Silvestri, Emmanuele Crespan, Giuseppe La Regina
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2020)
Article
Biochemistry & Molecular Biology
Milosz Rolinski, Nicola Pietro Montaldo, Merdane Ezgi Aksu, Sarah L. Fordyce Martin, Alessandro Brambilla, Nicolas Kunath, Jostein Johansen, Sten Even Erlandsen, Nina-Beate Liabbak, Kristin Rian, Magnar Bjoras, Pal Saetrom, Barbara van Loon
Summary: The research identified a novel mechanism of alkylation stress response dependent on MED13 and cyclin D1, which can serve as a basis for developing innovative therapeutic strategies.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Maria Dede, Silvia Napolitano, Anna Melati, Valentina Pirota, Giovanni Maga, Emmanuele Crespan
Summary: Ribonucleotides misincorporated in the human genome are the most common DNA lesions and can lead to strand breaks and replicative fork stalling. The enzyme RNase H2 plays a key role in removing these ribonucleotides, but its activity can be severely impaired by certain DNA structures, highlighting the significance of misincorporated ribonucleotides in the physiological instability of specific DNA sequences.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Valentina Pirota, Enrico Lunghi, Alessandra Benassi, Emmanuele Crespan, Mauro Freccero, Filippo Doria
Summary: The study demonstrated the selective interaction of two new Cu(II)-NDI complexes towards parallel G4 structures, providing promising results for the development of new selective functional ligands for binding and restructuring parallel G4s.
Article
Oncology
Annalaura Brai, Valentina Riva, Letizia Clementi, Lucia Falsitta, Claudio Zamperini, Virginia Sinigiani, Claudio Festuccia, Samantha Sabetta, Davide Aiello, Camilla Roselli, Anna Garbelli, Claudia Immacolata Trivisani, Laura Maccari, Francesca Bugli, Maurizio Sanguinetti, Pierpaolo Calandro, Mario Chiariello, Paola Quaranta, Lorenzo Botta, Adriano Angelucci, Giovanni Maga, Maurizio Botta
Summary: In the last decade, the human helicase protein DDX3X has emerged as a promising target for anticancer drug development. A novel inhibitor, BA103, has shown broad-spectrum anticancer activity by targeting DDX3X's helicase binding site. BA103 exhibited good tolerability, pharmacokinetic properties, and potential for inhibiting tumor growth and migration, especially in glioblastoma models. This study demonstrates the feasibility and promise of DDX3X-targeted small molecules as potential drugs for treating various cancers, including glioblastoma.
Article
Chemistry, Medicinal
Maria Grazia Martina, Filomena Sannio, Emmanuele Crespan, Marialaura Pavone, Alice Simoncini, Francesca Barbieri, Cecilia Perini, Emanuela Pesce, Giovanni Maga, Nicoletta Pedemonte, Jean-Denis Docquier, Marco Radi
Summary: CF is a genetic disease caused by mutations in the CFTR gene, leading to negative effects on multiple organs, particularly accumulation of thick mucus in the lungs and chronic respiratory infections. Lung function decline is associated with bacterial infections requiring antibiotic treatments. Developing multifunctional antibiotics tailored to CF may simplify therapeutic approach.
Review
Oncology
Massimiliano Secchi, Camilla Lodola, Anna Garbelli, Silvia Bione, Giovanni Maga
Summary: The transformation of a normal cell into a cancerous one is caused by the deregulation of metabolic pathways and protein-protein interactions. Cellular enzymes DDX3X and DDX5 play important roles in normal cell metabolism, but their deregulation can accelerate tumor transformation. This review summarizes the roles of DDX3X and DDX5 in different tumors and discusses their protein-protein interactions in cancer proliferation.
Article
Agriculture, Dairy & Animal Science
L. Bittner-Schwerda, E. Malama, M. Siuda, B. van Loon, H. Bollwein
Summary: This study investigated the effects of hydrogen peroxide (H2O2) on the chromatin structure of sperm. The results showed that H2O2 adversely affected the sperm's motility, plasma membrane and acrosome integrity, but had a minor impact on chromatin structure. The addition of catalase reversed the chromatin damage caused by H2O2.
ANIMAL REPRODUCTION SCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Silvia Cesarini, Ilaria Vicenti, Federica Poggialini, Massimiliano Secchi, Federica Giammarino, Ilenia Varasi, Camilla Lodola, Maurizio Zazzi, Elena Dreassi, Giovanni Maga, Lorenzo Botta, Raffaele Saladino
Summary: Current therapy against SARS-CoV-2 relies on Remdesivir, Molnupiravir, and Nirmatrelvir, but they have limitations. By synthesizing and evaluating derivatives, a promising compound with antiviral activity and low cytotoxicity was identified as a candidate for future optimization studies.
Article
Biochemistry & Molecular Biology
Sunbok Jang, Namrata Kumar, Mathew A. Schaich, Zhou Zhong, Barbara van Loon, Simon C. Watkins, Bennett Van Houten
Summary: This study discovered that UV-DDB has specific recognition for N-6-ethenoadenine and hypoxanthine, besides oxidized bases, and it stimulates AAG activity and helps with the release of AAG from abasic sites, facilitating the repair process.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Pharmacology & Pharmacy
Federica Poggialini, Chiara Vagaggini, Annalaura Brai, Claudia Pasqualini, Emmanuele Crespan, Giovanni Maga, Cecilia Perini, Noemi Cabella, Lorenzo Botta, Francesca Musumeci, Maria Frosini, Silvia Schenone, Elena Dreassi
Summary: In this study, a series of pyrazolo[3,4-d]pyrimidine derivatives from an in-house library were evaluated for their potential as therapeutic candidates against glioblastoma. Compound 5 demonstrated promising inhibitory activity against c-Src and Abl, significant antiproliferative effects on GBM cell lines, and low toxicity towards healthy cells. These findings highlight compound 5 as a potential treatment for further in vivo assays.
Article
Chemistry, Medicinal
Claudia Contadini, Claudia Cirotti, Anna Carbone, Mehrdad Norouzi, Annarita Cianciusi, Emmanuele Crespan, Cecilia Perini, Giovanni Maga, Daniela Barila, Francesca Musumeci, Silvia Schenone
Summary: This article discusses the role of Src in cancer, including glioblastoma. The researchers synthesized a series of derivatives and identified SI388 as the most potent Src inhibitor. SI388 not only inhibits cancer cell growth, but also enhances sensitivity to radiation.
Article
Cell Biology
Rossana Aprigliano, Merdane Ezgi Aksu, Stefano Bradamante, Boris Mihaljevic, Wei Wang, Kristin Rian, Nicola P. Montaldo, Kayla Mae Grooms, Sarah L. Fordyce Martin, Diana L. Bordin, Matthias Bosshard, Yunhui Peng, Emil Alexov, Cindy Skinner, Nina-Beate Liabakk, Gareth J. Sullivan, Magnar Bjoras, Charles E. Schwartz, Barbara van Loon
Summary: The study reveals that increased p53 signaling due to HUWE1 mutations is central to XLID syndromes, particularly affecting neural differentiation in JMS cells. By reducing p53 levels and restoring p53 target gene expression, the neural differentiation defects in JMS cells can be successfully rescued.
CELL REPORTS MEDICINE
(2021)