Article
Multidisciplinary Sciences
Dean Huang, Anna E. Johnson, Brandon S. Sim, Teresa W. Lo, Houra Merrikh, Paul A. Wiggins
Summary: Quantitative characterization of nucleic-acid-bound molecular motors' dynamics in living cells is crucial for understanding the mechanistic basis of the central dogma. Lag-time analysis was developed to measure in vivo dynamics, providing quantitative locus-specific measurements of fork velocity and replisome pause durations. The observed dynamics are both locus and time dependent, even in wild-type cells, showing locus-specific pauses and temporal fork velocity oscillations.
NATURE COMMUNICATIONS
(2023)
Article
Genetics & Heredity
Julien Brochu, Emilie Vlachos-Breton, Dina Irsenco, Marc Drolet
Summary: DNA topoisomerases are essential for solving topological problems in DNA structure during replication, transcription, and recombination. The absence of type IA topoisomerases leads to unregulated replication from R-loops, causing genome instability. Our study reveals a pathway of genomic instability triggered by R-loops and its regulation by various topoisomerases.
Article
Virology
Lei Zhang, Yuekun Shao, Yingying Wang, Qiuxian Yang, Jiamei Guo, George F. Gao, Tao Deng
Summary: The last amino acid I121 of the viral NS2 protein plays a critical role in promoting viral genome replication. The hydrophobicity of residue 121 is essential for virus survival. Adaptive mutations PA-K19E and PB1-S713N compensate for the replication-promoting defect caused by NS2-I121 mutation.
JOURNAL OF VIROLOGY
(2023)
Article
Genetics & Heredity
Diwaker Tripathi, Delene J. Oldenburg, Arnold J. Bendich
Summary: The genome sequences of maize ptDNA were determined for four different tissues, and compared to the reference genome sequence. The sequences were found to be identical among the tissues, but there were more variants in leaves grown in the dark. These variants were clustered in specific regions of the plastid genome, and replication-transcription conflict could be the cause.
FRONTIERS IN GENETICS
(2022)
Article
Biochemistry & Molecular Biology
Lia M. Pinto, Alexandros Pailas, Max Bondarchenko, Abhishek Bharadwaj Sharma, Katrin Neumann, Anthony J. Rizzo, Celine Jeanty, Nathalie Nicot, Carine Racca, Mindy K. Graham, Catherine Naughton, Yaqun Liu, Chun-Long Chen, Paul J. Meakin, Nick Gilbert, Sebastien Britton, Alan K. Meeker, Christopher M. Heaphy, Florence Larminat, Eric Van Dyck
Summary: Maintaining chromatin integrity at centromeres is crucial for preventing DNA breaks and genomic instability. The histone chaperone complex ATRX/DAXX is involved in establishing and maintaining centromeric chromatin structure. We discovered a novel ATRX-independent function for DAXX in promoting genome stability by preventing R-loop accumulation and DNA double-strand break formation at centromeres.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Chao Liu, Wei Xu, Liying Wang, Zhuo Yang, Kuan Li, Jun Hu, Yinghong Chen, Ruidan Zhang, Sai Xiao, Wenwen Liu, Huafang Wei, Jia-Yu Chen, Qianwen Sun, Wei Li
Summary: During yeast meiosis, the frequency and distribution of R-loops, a type of chromatin structure, changed significantly. We found that multiple de novo R-loops were formed during the pachytene stage and were associated with meiotic recombination. The collisions between transcription and replication could promote the formation of R-loops during meiotic DNA replication, and these R-loops were associated with Spo11. Additionally, reversing the direction of transcription or replication could eliminate meiotic recombination hotspots, while reversing both directions could reconstitute the hotspots.
CELL AND BIOSCIENCE
(2023)
Review
Biology
Benjamin S. Simpson, Hayley Pye, Hayley C. Whitaker
Summary: Recent developments in sequencing the cancer genome have identified 16 signatures of structural variants across 38 tumour types, with some of the variants occurring at fragile sites like NAALADL2. These copy-number variations at fragile sites may have a significant impact on cell signalling.
COMMUNICATIONS BIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Laura Curti, Stefano Campaner
Summary: MYC is a transcription factor that controls the expression of a large fraction of cellular genes linked to cell cycle progression, metabolism and differentiation. Deregulation of MYC in tumors leads to pervasive genome-wide binding and selective transcriptional control of cellular genes, along with alterations in cell cycle control and DNA-replication landscape. This may pose as an intrinsic liability in MYC-overexpressing cancer cells, and triggering replicative stress in MYC-driven tumors shows therapeutic potential.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Genetics & Heredity
Adam Poti, Bernadett Szikriszt, Judit Zsuzsanna Gervai, Dan Chen, David Szuts
Summary: This study investigates the extent and genetic dependence of collateral mutagenesis in higher eukaryotes. The researchers find that collateral mutations frequently occur near primary lesions generated by cisplatin or ultraviolet radiation in chicken and human cells, but are restricted to a short distance of approximately 25 base pairs. They also show that collateral mutations can also occur near correctly bypassed primary lesions and may be responsible for a considerable proportion of all base substitution mutations.
Article
Biochemistry & Molecular Biology
Maheshi Udugama, Benjamin Vinod, F. Lyn Chan, Linda Hii, Andrew Garvie, Philippe Collas, Paul Kalitsis, David Steer, Partha P. Das, Pratibha Tripathi, Jeffrey R. Mann, Hsiao P. J. Voon, Lee H. Wong
Summary: In this study, researchers found that the phosphorylation of H3.3 at the S31 residue regulates heterochromatin accessibility at telomeres during replication. This process is achieved through the regulation of the histone demethylase KDM4B. Abnormal phosphorylation of H3.3 S31 can lead to altered H3K9me3 modification and subsequent DNA damage. The regulation of H3.3 S31Ph also affects the overall chromatin integrity of other heterochromatin regions.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Cell Biology
Eduardo Cararo-Lopes, Matheus H. Dias, Marcelo S. da Silva, Julianna D. Zeidler, Alexandre T. Vessoni, Marcelo S. Reis, Enrique Boccardo, Hugo A. Armelin
Summary: This study found that in HPV-infected cells, HRas(G12V) activity triggers highly transforming mitogenic signals, leading to strong replication and oxidative stress, which are counteracted by autophagy induction. Autophagy plays a crucial role in allowing the transition of E6E7 keratinocytes from an immortalized to a malignant state caused by HRas(G12V).
CELL DEATH & DISEASE
(2021)
Article
Biochemistry & Molecular Biology
Yunying Zhou, Jason J. Chen
Summary: STAT3 plays an important role in DNA replication, mediated by its newly identified target gene WDHD1. These studies have significant implications.
CELL AND BIOSCIENCE
(2021)
Article
Microbiology
Elona Gusho, Laimonis A. Laimins
Summary: cGAS is a critical regulator of the innate immune response and acts as a sensor for double-stranded DNA from pathogens or damaged host DNA. In HPV positive cells, cGAS levels are increased and it plays a role through various signaling pathways. The study also reveals the important role of cGAS in mediating the response of HPV positive cells to chemotherapeutic drugs.
Review
Medicine, Research & Experimental
Chengcheng Guan, Xintong Zhou, Huayao Li, Xiaoran Ma, Jing Zhuang
Summary: Polyphenol compounds, as natural antioxidants, have anti-inflammatory and antioxidant properties, and are believed to have various medicinal benefits for improving human health. Their anticancer effect is mainly attributed to their strong antioxidant and immunomodulatory effects. By targeting NF-KB, polyphenol compounds can exert antioxidant and immunomodulatory effects, hindering the occurrence and development of tumors. They have advantages over conventional anticancer therapies as they have minimal side effects and can attenuate the toxic effects of other treatments, showing great potential in cancer prevention and treatment.
BIOMEDICINE & PHARMACOTHERAPY
(2022)
Article
Biochemistry & Molecular Biology
Kathleen M. Urrutia, Wenyan Xu, Linlin Zhao
Summary: In higher eukaryotes, mitochondria play multiple roles in energy production, signaling, and biosynthesis. Mitochondria possess multiple copies of mitochondrial DNA (mtDNA), which encodes 37 genes that are essential for mitochondrial and cellular function. The human mitochondrial genome maintenance exonuclease 1 (MGME1) is a key factor involved in mtDNA degradation. This study examines the effects of substrate structure and sequence on the enzymatic activities of MGME1 and provides insights into its properties.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Ahmed Aljohani, Mohammad Imran Khan, Abram Bonneville, Changan Guo, Justin Jeffery, Lucas O'Neill, Deeba Nadeem Syed, Sarah A. Lewis, Maggie Burhans, Hasan Mukhtar, James M. Ntambi
JOURNAL OF BIOLOGICAL CHEMISTRY
(2019)
Article
Biochemistry & Molecular Biology
Brent W. Anderson, Aili Hao, Kenneth A. Satyshur, James L. Keck, Jue D. Wang
JOURNAL OF MOLECULAR BIOLOGY
(2020)
Article
Microbiology
Bret N. Peterson, Megan K. M. Young, Shukun Luo, Jeffrey Wang, Aaron T. Whiteley, Joshua J. Woodward, Liang Tong, Jue D. Wang, Daniel A. Portnoy
Article
Multidisciplinary Sciences
Jin Yang, Brent W. Anderson, Asan Turdiev, Husan Turdiev, David M. Stevenson, Daniel Amador-Noguez, Vincent T. Lee, Jue D. Wang
NATURE COMMUNICATIONS
(2020)
Review
Genetics & Heredity
Jeremy W. Schroeder, T. Sabari Sankar, Jue D. Wang, Lyle A. Simmons
Article
Microbiology
Danny K. Fung, Jin Yang, David M. Stevenson, Daniel Amador-Noguez, Jue D. Wang
FRONTIERS IN MICROBIOLOGY
(2020)
Article
Public, Environmental & Occupational Health
Yuexin Dong, Ba Dun, Pu Bu Wang Dui, Luo Bu Zhuo, Jie Fang, Ci Ren Yang Zong, Zong Ji, Pengpeng Xu, Yu Zheng, Fei Yue, Junmin Li, Xiaoyang Li
WILDERNESS & ENVIRONMENTAL MEDICINE
(2020)
Article
Biology
Taylor B. Updegrove, Jailynn Harke, Vivek Anantharaman, Jin Yang, Nikhil Gopalan, Di Wu, Grzegorz Piszczek, David M. Stevenson, Daniel Amador-Noguez, Jue D. Wang, L. Aravind, Kumaran S. Ramamurthi
Summary: Hydrolysis of nucleoside triphosphates releases similar amounts of energy, with ATP typically used for energy-intensive reactions and GTP serving as a switch. The bacterial cytoskeletal protein SpoIVA, evolved from a TRAFAC class of P-loop GTPases, failed to polymerize after reengineering its nucleotide-binding pocket to mimic ancestral GTPase activity, highlighting the critical role of the nucleotide base in specific biological functions. The evolutionary pressure that drove the change in nucleotide preference in SpoIVA was suggested to be increased levels of ATP relative to GTP at the end of sporulation.
Review
Genetics & Heredity
Brent W. Anderson, Danny K. Fung, Jue D. Wang
Summary: This article focuses on the important regulatory role of (p)ppGpp in bacterial metabolism, inducing rapid and coordinated changes in cellular metabolism by regulating enzymatic activities, and how (p)ppGpp and other nucleotides directly regulate metabolic remodeling. Research highlights the key role of (p)ppGpp in bacterial adaptation to their environmental niches.
ANNUAL REVIEW OF GENETICS, VOL 55
(2021)
Article
Biochemistry & Molecular Biology
Christina N. Giramma, McKenna B. DeFoer, Jue D. Wang
Summary: Primase plays a crucial role in DNA replication by synthesizing RNA primers, and its activity in bacteria can be regulated by (p)ppGpp. The presence of (p)ppGpp in Bacillus subtilis inhibits DNA replication, particularly primer extension, to ensure genome stability under environmental stress. High levels of (p)ppGpp, combined with low GTP concentration, effectively suppress primase activity in B. subtilis.
JOURNAL OF MOLECULAR BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Brent W. Anderson, Maria A. Schumacher, Jin Yang, Asan Turdiev, Husan Turdiev, Jeremy W. Schroeder, Qixiang He, Vincent T. Lee, Richard G. Brennan, Jue D. Wang
Summary: This study reveals a novel mechanism of gene regulation by (p)ppGpp in Firmicutes, where (p)ppGpp directly binds to the transcription factor PurR to downregulate purine biosynthesis gene expression upon amino acid starvation. The findings demonstrate the crucial role of (p)ppGpp in regulating nucleotide synthesis through gene regulation, from soil bacteria to pathogens.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Microbiology
Pietro Giammarinaro, Megan K. M. Young, Wieland Steinchen, Christopher-Nils Mais, Georg Hochberg, Jin Yang, David M. Stevenson, Daniel Amador-Noguez, Anja Paulus, Jue D. Wang, Gert Bange
Summary: This study identifies the molecular mechanism by which Ap4A regulates IMPDH and GTP production in Bacillus subtilis. It also highlights the central role of IMPDH in metabolism remodeling and heat resistance.
NATURE MICROBIOLOGY
(2022)
Article
Microbiology
Danny K. K. Fung, Kaihong Bai, Jin Yang, Xiaoli Xu, David M. M. Stevenson, Daniel Amador-Noguez, Laixin Luo, Jue D. D. Wang
Summary: This study reveals the regulatory role of bacterial SAHs in stress responses and metabolism. XccSAH hydrolyzes multiple nucleotides in vitro and X. campestris pv. campestris mutants lacking sah accumulate higher levels of (pp)pGpp and NADPH during starvation. Additionally, the mutants are more sensitive to killing by Pseudomonas and show reduced growth. This work provides insights into the physiological functions of bacterial SAHs beyond their role as antitoxins.
Article
Multidisciplinary Sciences
Jeremy W. W. Schroeder, Rebecca L. L. Hurto, Justin R. R. Randall, Katherine J. J. Wozniak, Taylor A. A. Timko, Taylor M. M. Nye, Jue D. D. Wang, Peter L. L. Freddolino, Lyle A. A. Simmons
Summary: RNA:DNA hybrids hinder replication fork progression and compromise genome integrity in all cells. The impact of naturally occurring hybrids on genome integrity and the role of ribonucleases H in mitigating their negative effects are unknown. This study investigates the contributions of RNases HII and HIII to hybrid removal, DNA replication, and mutagenesis across the genome. Deletion of rnhB or rnhC leads to RNA:DNA hybrid accumulation with different patterns of mutagenesis and hybrid distribution. Hybrids mainly accumulate in noncoding RNAs and 5'-UTRs of coding sequences. In ?rnhB cells, hybrids preferentially accumulate in untranslated regions and early in coding sequences. Gene expression levels significantly affect hybrid accumulation in ?rnhC cells. Disruption of DNA replication in ?rnhC cells leads to transversions and structural variation. These findings provide insights into how hybrids cause mutagenesis and shape genome organization in native genomic contexts.