Article
Cell Biology
Adhirath Sikand, Malgorzata Jaszczur, Linda B. Bloom, Roger Woodgate, Michael M. Cox, Myron F. Goodman
Summary: The study investigates the role of a specialized error-prone DNA polymerase in Escherichia coli and the impact of the beta-sliding processivity clamp on DNA synthesis efficiency. Results suggest that beta clamp enhances primer elongation and translesion DNA synthesis, possibly by stabilizing the polymerase and inhibiting its ATPase activity.
Article
Biology
Fengwei Zheng, Roxana Georgescu, Nina Y. Yao, Huilin Li, Michael E. O'Donnell
Summary: The RFC complex has been shown to have a second DNA binding site, located between the N-terminal BRCT domain and AAA+ module of the large Rfc1 subunit. This 5' DNA site exhibits ideal binding to a 7-nt gap and shows enhanced binding to 5 and 10 nt gaps. It is proposed that the 5' site facilitates RFC's PCNA loading activity at DNA damage-induced gaps and plays a potential role in lagging strand DNA synthesis.
Article
Microbiology
Tommy F. Tashjian, Peter Chien
Summary: Different species of bacteria have developed different mechanisms to produce DnaX tau and gamma forms, suggesting the importance of having two forms of DnaX. DnaX is critical for the processivity of DNA polymerase and coordinating synthesis on the leading and lagging strands. Despite being discovered over 30 years ago, the purpose of expressing both tau and gamma forms is still unclear. This study provides evidence that expressing two forms of DnaX and controlling their abundance and/or ratio is important during the resolution of DNA replication stress.
JOURNAL OF BACTERIOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Kevin M. Wernke, Alina Tirla, Mengzhao Xue, Yulia Surovtseva, Fabian S. Menges, Seth B. Herzon
Summary: Colibactin is a genotoxic metabolite produced by commensal-pathogenic members of the human microbiome, potentially linked to tumorigenesis. Researchers synthesized and studied colibactin 742 (4), finding that it induces DNA interstrand-cross-links and activates DNA repair pathways, providing a new approach to study the genotoxic effects of colibactin.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Microbiology
Camille Chagneau, Clemence Massip, Nadege Bossuet-Greif, Christophe Fremez, Jean-Paul Motta, Ayaka Shima, Celine Besson, Pauline Le Faouder, Nicolas Cenac, Marie-Paule Roth, Helene Coppin, Maxime Fontanie, Patricia Martin, Jean-Philippe Nougayrede, Eric Oswald
Summary: This study found the presence of the genotoxin Colibactin in the urine of patients with urinary tract infections, and demonstrated its genotoxicity in bladder cells. This discovery raises the hypothesis of a potential link between urinary tract infections and bladder cancer.
Article
Gastroenterology & Hepatology
Nadege Bossuet, Cecile Guyonnet, Camille Chagneau, Min Tang-Fichaux, Marie Penary, Dorian Loubet, Priscilla Branchu, Eric Oswald, Jean-Philippe Nougayrede
Summary: Up to 25% of healthy human feces-derived E. coli strains carry the pks genomic island, which is responsible for synthesizing colibactin, a genotoxic compound implicated in colorectal cancer. However, the expression conditions of colibactin in the gut remain poorly understood. In this study, it is demonstrated that colibactin production is highest under anoxic conditions and decreases with increased oxygen concentration. The positive regulation of colibactin production and genotoxicity by the aerobic respiration control (ArcA) in response to oxygen availability suggests that the pks biosynthetic pathway is adapted for the anoxic intestinal lumen and hypoxic infected or tumor tissue.
Editorial Material
Biochemistry & Molecular Biology
David Jeruzalmi
Summary: Eukaryotes possess various clamp loaders, each with four common subunits and a unique fifth subunit. The RFC-A-E clamp loader loads the PCNA clamp at 3'-recessed DNA structures, while swapping the Rad24 subunit for RFC-A results in a loader that prefers the 911 clamp and 5'-recessed DNA. Recent studies provide detailed insights into the clamp loading reaction and substrate preferences of each loader.
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2022)
Review
Biochemistry & Molecular Biology
David A. Gillespie
Summary: Two recent reports demonstrate that heritable, gain-of-function mutations within the Chk1 C-terminal regulatory domain can cause female infertility. Treatment with selective Chk1 inhibitor drugs can rescue this mutation and allow embryos to develop normally.
Article
Oncology
Sophie Gilbert, Benjamin Peant, Anne-Marie Mes-Masson, Fred Saad
Summary: Inhibition of IKK-epsilon expression or using IKK-epsilon inhibitors can decrease proliferation and tumor volume of castrate resistant prostate cancer cells. Moreover, these inhibitors can induce senescence, DNA damage, and genomic instability. Combining Amlexanox and Olaparib can enhance the anti-cancer effects.
Article
Biochemistry & Molecular Biology
Mohd Farhan, Asim Rizvi, Aamir Ahmad, Mohammad Aatif, Mir Waqas Alam, Sheikh Mumtaz Hadi
Summary: The possible roles of elevated endogenous copper levels in malignant cells are becoming increasingly understood. Tea catechins have the ability to mobilize endogenous copper and selectively damage cancer cells. Cellular copper transporters CTR1 and ATP7A play a role in the survival dynamics of malignant cells post-tea catechin exposure.
Article
Biochemistry & Molecular Biology
Owen Davis Sanders, Lekshmy Rajagopal, Jayalekshmi Archa Rajagopal
Summary: The amyloid-beta oligomer hypothesis of Alzheimer's disease remains dominant in the field, but clinical trial evidence does not strongly support it. To rescue the hypothesis, researchers propose a new ad-hoc hypothesis suggesting that the vulnerable hippocampus may produce A beta peptides even in healthy aging individuals, and DNA damage, pathogens, and metal ions may drive A beta peptide aggregation and contribute to neurodegeneration in AD.
FREE RADICAL BIOLOGY AND MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Hrishita Das, Sukanya Sarkar, Ramesh K. Paidi, Subhas C. Biswas
Summary: Accumulation of amyloid-beta in the brain is a major trigger for Alzheimer's disease pathogenesis. Mild DNA damage leads to increased production of Aβ. Mitochondrial fusion and the protein MFN2 play a role in this process, potentially as an adaptive response to ER stress, which may contribute to increased Aβ production.
Article
Oncology
Min Zhang, Zhi Dai, Xudong Zhao, Gan Wang, Ren Lai
Summary: The study demonstrated that anticarin beta can effectively suppress proliferation and induce apoptosis in glioma cells, decrease stemness gene expression, induce DNA damage, and eventually lead to apoptosis by regulating oncogene expression. Overall, anticarin beta shows promising potential as an inhibitor for malignant glioma.
FRONTIERS IN ONCOLOGY
(2021)
Review
Oncology
Ya Wang, Kai Fu
Summary: Colorectal cancer (CRC) is a major cause of cancer-related death worldwide, with an increasing incidence in developing areas. Bacterial pathogens from the gut microbiota, particularly Escherichia coli (E. coli), are recognized as significant risk factors for CRC. This review provides an update on the knowledge of E. coli-produced genotoxins associated with CRC. It discusses the various genotoxins produced by E. coli, their mechanisms of action, and their potential to induce tumorigenesis through DNA damage and cellular responses.
Article
Oncology
Melvin E. Thomas, Sherif Abdelhamed, Ryan Hiltenbrand, Jason R. Schwartz, Sadie Miki Sakurada, Michael Walsh, Guangchun Song, Jing Ma, Shondra M. Pruett-Miller, Jeffery M. Klco
Summary: Pediatric myelodysplastic syndromes (MDS) are associated with impaired hematopoiesis, bone marrow hypocellularity, and deletions involving chromosome 7 (monosomy 7). Mutations in SAMD9 and SAMD9L lead to alterations in cell cycle, cell proliferation, and protein translation in HSPCs, potentially causing DNA damage repair defects and apoptosis in hematopoietic cells.
Article
Biochemistry & Molecular Biology
Monica C. Pillon, Vignesh M. P. Babu, Justin R. Randall, Jiudou Cai, Lyle A. Simmons, Mark D. Sutton, Alba Guarne
NUCLEIC ACIDS RESEARCH
(2015)
Article
Biochemistry & Molecular Biology
Vignesh M. P. Babu, Mark Itsko, Jamie C. Baxter, Roel M. Schaaper, Mark D. Sutton
MOLECULAR MICROBIOLOGY
(2017)
Article
Biochemistry & Molecular Biology
Jin S. Kim, Michael T. Nanfara, Sundari Chodavarapu, Kyeong S. Jin, Vignesh M. P. Babu, Mohamed A. Ghazy, Scisung Chung, Jon M. Kaguni, Mark D. Sutton, Yunje Cho
NUCLEIC ACIDS RESEARCH
(2017)
Article
Microbiology
Anubrata Ghosal, Vignesh M. P. Babu, Graham C. Walker
JOURNAL OF BACTERIOLOGY
(2018)
Article
Multidisciplinary Sciences
Vignesh M. P. Babu, Mark D. Sutton
Article
Biochemistry & Molecular Biology
Vignesh M. P. Babu, Siva Sankari, James A. Budnick, Clayton C. Caswell, Graham C. Walker
NUCLEIC ACIDS RESEARCH
(2020)
Article
Microbiology
Vignesh M. P. Babu, Caleb Homiski, Michelle K. Scotland, Sundari Chodavarapu, Jon M. Kaguni, Mark D. Sutton
Summary: The mutation in the dnaN(E202K) allele leads to underinitiation of DNA replication due to heightened Hda activity and altered levels of multiple DnaA-regulated genes. While in vitro experiments show similar Hda activity levels between beta(E202K) and wild-type clamp proteins, co-overexpression of RNR relieved the growth defect caused by elevated clamp levels. These results suggest that increased levels of DNA precursors can alleviate the growth inhibitory effects of elevated beta clamp levels.
JOURNAL OF BACTERIOLOGY
(2021)
Article
Microbiology
Caleb Homiski, Michelle K. Scotland, Vignesh M. P. Babu, Sundari Chodavarapu, Robert W. Maul, Jon M. Kaguni, Mark D. Sutton
Summary: This study demonstrates that overexpression of the Escherichia coli dnaN-encoded beta clamp inhibits cell growth by interfering with DNA replication. A mutant beta clamp, beta(E202K), was identified to effectively sequester Pol III in vivo but showed defects in DNA replication in vitro. The findings provide insights into the interactions and management of E. coli DNA polymerases II, III, and IV by the beta clamp.
JOURNAL OF BACTERIOLOGY
(2021)
Article
Microbiology
Charley C. Gruber, Vignesh M. P. Babu, Kamren Livingston, Heer Joisher, Graham C. Walker
Summary: Incomplete base excision repair (BER) induced by oxidative stress plays a significant role in bacterial cell death, but its contribution varies greatly depending on different lethal stresses and physiological changes experienced by the cells.
Article
Microbiology
Vignesh M. P. Babu, Siva Sankari, Anubrata Ghosal, Graham C. Walker
Summary: This study provides insights into the roles of Era and YbeY in ribosome assembly and 16S rRNA processing, and identifies that the T99I mutation can partially suppress the pleiotropic phenotypes caused by ybeY deletion.
FRONTIERS IN MICROBIOLOGY
(2022)
Article
Microbiology
Siva Sankari, Vignesh M. P. Babu, Ke Bian, Areej Alhhazmi, Mary C. Andorfer, Dante M. Avalos, Tyler A. Smith, Kwan Yoon, Catherine L. Drennan, Michael B. Yaffe, Sebastian Lourido, Graham C. Walker
Summary: Symbiotic partnership with rhizobial bacteria allows legumes to grow without nitrogen fertilizer. Legumes produce peptides that bind haem to reduce its availability, inducing iron-starvation response in rhizobia, which is required for nitrogenase activity.
NATURE MICROBIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Anubrata Ghosal, Caroline Kohrer, Vignesh M. P. Babu, Kinrin Yamanaka, Bryan W. Davies, Asha I. Jacob, Daniel J. Ferullo, Charley C. Gruber, Maarten Vercruysse, Graham C. Walker
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2017)
Article
Biotechnology & Applied Microbiology
S. Ramalingam, M. Vikram, M. P. Vigneshbabu, M. Sivasankari
INDIAN JOURNAL OF BIOTECHNOLOGY
(2011)