Review
Microbiology
Joana Faria, Emma M. Briggs, Jennifer A. Black, Richard McCulloch
Summary: The survival and transmission of the African trypanosome rely on antigenic variation, which involves stochastic changes in the composition of their protective VSG coat. This process can be executed through transcriptional or recombination reactions. Understanding the cellular machinery behind this process is crucial for potential interventions.
CURRENT OPINION IN MICROBIOLOGY
(2022)
Article
Multidisciplinary Sciences
Arthur J. Lustig
Summary: An in silico study of Aspergillus flavus genome stability revealed significant variations in coding and non-coding regions. Non-coding insertions consisted of AT-rich sequences distributed at different sites in different strains. Two major categories of AT-rich elements (ATEs) in non-centromeric regions were identified: homologous insertions containing transposable elements (TEs) and a conserved set of subtelomeric ATE repeats. Centromeric ATEs and TE clusters displayed a high level of sequence identity between strains, suggesting their role in the evolution of subtelomeric and centromeric structure and function.
Article
Multidisciplinary Sciences
Donna R. Whelan, Eli Rothenberg
Summary: Using single-molecule localization super-resolution imaging assays, we observed the spatiotemporal behavior of key mediator and nuclease proteins during DNA resection at single-ended double-strand breaks. Multiple simultaneous resection events were demonstrated, with recruitment of various proteins and completion of resection 2 to 4 hours after break induction. Additionally, we identified potential roles of BRCA1 and BLM in homology search and repair resolution during HR.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Review
Parasitology
Joana R. C. Faria
Summary: African trypanosomes are early divergent protozoan parasites responsible for high mortality and morbidity as well as a great economic burden among the world's poorest populations. Understanding the mechanisms underpinning antigen as well as general gene expression control is crucial for designing effective control strategies against these organisms. Recent technological developments have advanced our understanding of nuclear organization and gene expression control in trypanosomes, opening novel research avenues.
Article
Cell Biology
Ilaria Ceppi, Elda Cannavo, Helene Bret, Rosa Camarillo, Francesca Vivalda, Roshan Singh Thakur, Amador Romero-Franco, Alessandro A. Sartori, Pablo Huertas, Raphael Guerois, Petr Cejka
Summary: In this study, the researchers used AlphaFold2 to identify a separation-of-function mutant of CtIP, CtIP-F728E-Y736E, which can still work with MRN but cannot stimulate ssDNA degradation by DNA2. The findings support a model in which the phosphorylation of CtIP by CDK activates DNA resection in the S phase, while the phosphorylation of CtIP by PLK1 disrupts its stimulation of DNA2, attenuating long-range resection later in the cell cycle.
GENES & DEVELOPMENT
(2023)
Article
Multidisciplinary Sciences
Maciej Majka, Eva Janakova, Irena Jakobson, Kadri Jarve, Petr Capal, Zuzana Korchanova, Adam Lampar, Jakub Juracka, Miroslav Valarik
Summary: For the first time, this study investigates the sequence and epigenetic differences between a wheat recombination hotspot (H1) and a regular recombination site (Rec7) under conditions with functional and non-functional Ph1 loci. The results provide valuable insights into chromatin landmarks associated with specific recombination sites and deepen the understanding of the role of the Ph1 locus in wheat recombination processes.
JOURNAL OF ADVANCED RESEARCH
(2023)
Review
Parasitology
Sara Silva Pereira, Andrew P. Jackson, Luisa M. Figueiredo
Summary: An intriguing and remarkable feature of African trypanosomes is their antigenic variation system, mediated by the variant surface glycoprotein (VSG) family. Recent studies have revealed that the VSG repertoire has a complex evolutionary history and plays a key role in immune evasion and disease epidemiology. The diversity in sequence, genomic organization, and expression patterns within the VSG family may explain variations in parasite virulence and disease pathology, indicating a need for further exploration of their functional roles.
TRENDS IN PARASITOLOGY
(2022)
Article
Multidisciplinary Sciences
Jinhua Han, Li Wan, Guixing Jiang, Liping Cao, Feiyu Xia, Tian Tian, Xiaomei Zhu, Mingjie Wu, Michael S. Y. Huen, Yi Wang, Ting Liu, Jun Huang
Summary: This study identifies a novel regulatory mechanism that modulates the activity of CtIP at DSBs and the extent of end resection through ATM-dependent sequential posttranslational modification of CtIP.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Multidisciplinary Sciences
Xuanpeng Wang, Lili Wang, Yongchi Huang, Zhiping Deng, Cunliang Li, Jian Zhang, Mingxi Zheng, Shunping Yan
Summary: This study reveals the important role of a plant-specific ubiquitin E3 ligase, DDRM1, in homologous recombination repair (HR), which is essential for maintaining genome stability. DDRM1 interacts with and ubiquitinates the transcription factor SOG1, promoting its stability. This research uncovers the regulatory mechanism of HR in plants and highlights the significance of ubiquitination in HR.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biology
Michael T. Kimble, Matthew J. Johnson, Mattie R. Nester, Lorraine S. Symington
Summary: Exo1 and Sgs1 are involved in long-range resection during HR, which is connected to the activation of the DNA damage checkpoint and the mobility of chromosomes.
Article
Multidisciplinary Sciences
Artem Lisachov, Katerina Tishakova, Svetlana Romanenko, Lada Lisachova, Guzel Davletshina, Dmitry Prokopov, Lukas Kratochvil, Patricia O'Brien, Malcolm Ferguson-Smith, Pavel Borodin, Vladimir Trifonov
Summary: Research suggests that the cessation of recombination on sex chromosomes in geckos may be due to pre-existing recombination patterns and chromosomal rearrangements, which are largely neutral processes.
SCIENTIFIC REPORTS
(2023)
Article
Multidisciplinary Sciences
Tianpeng Zhang, Yashpal Rawal, Haoyang Jiang, Youngho Kwon, Patrick Sung, Roger A. Greenberg
Summary: Break-induced telomere synthesis (BITS) is a RAD51-independent mechanism that contributes to alternative lengthening of telomeres. This process utilizes a minimal replisome comprising PCNA and DNA polymerase-d to perform conservative DNA repair synthesis over long stretches. The response of this repair synthesis to complex secondary DNA structures and whether additional DNA repair events are orchestrated by the break-induced replisome remain unclear. In this study, the telomeric DNA damage response proteome during BITS was captured using a combination of synchronous double-strand break induction and proteomics of isolated chromatin segments (PICh). The findings revealed a replication stress-dominant response, with repair synthesis-driven DNA damage tolerance signaling through RAD18-dependent PCNA ubiquitination. The SNM1A nuclease was identified as the major effector of ubiquitinated PCNA-dependent DNA damage tolerance, playing a critical role in resection-dependent lesion bypass in mammalian cells.
Article
Oncology
Alessandro Testori, Zalman Vaksman, Sharon J. Diskin, Hakon Hakonarson, Mario Capasso, Achille Iolascon, John M. Maris, Marcella Devoto
Summary: Neuroblastoma is less common in African American children, but they more frequently develop the high-risk form of the disease. The study suggests that several common variants contribute to neuroblastoma risk in an ancestry-specific fashion.
CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
(2022)
Article
Biochemistry & Molecular Biology
Dan Sun, Thomas S. Layman, Hyeonsoo Jeong, Paramita Chatterjee, Kathleen Grogan, Jennifer R. Merritt, Donna L. Maney, Soojin V. Yi
Summary: Research has shown significant differences in DNA methylation between different developmental stages in wild white-throated sparrows, with differential methylation primarily involving genes related to development and cell differentiation. Differential methylation between plumage morphs is concentrated in the nonrecombining chromosome pair. Additionally, methylation reprogramming on the nonrecombining chromosome is associated with gene expression divergence.
Article
Plant Sciences
Alejandro Penafiel-Ayala, Antolin Peralta-Castro, Josue Mora-Garduno, Paola Garcia-Medel, Angie G. Zambrano-Pereira, Corina Diaz-Quezada, Maria Jazmin Abraham-Juarez, Claudia G. Benitez-Cardoza, Daniel B. Sloan, Luis G. Brieba
Summary: MutS HOMOLOG 1 (MSH1) is an organellar-targeted protein that obstructs ectopic recombination and the accumulation of mutations in plant organellar genomes. It also modulates the epigenetic status of nuclear DNA and prevents recombination between short repeats.
PLANT AND CELL PHYSIOLOGY
(2023)
Article
Chemistry, Medicinal
Victoriano Corpas-Lopez, Sonia Moniz, Michael Thomas, Richard J. Wall, Leah S. Torrie, Dorothea Zander-Dinse, Michele Tinti, Stephen Brand, Laste Stojanovski, Sujatha Manthri, Irene Hallyburton, Fabio Zuccotto, Paul G. Wyatt, Manu De Rycker, David Horn, Michael A. J. Ferguson, Joachim Clos, Kevin D. Read, Alan H. Fairlamb, Ian H. Gilbert, Susan Wyllie
ACS INFECTIOUS DISEASES
(2019)
Article
Biochemistry & Molecular Biology
Anna Trenaman, Lucy Glover, Sebastian Hutchinson, David Horn
NUCLEIC ACIDS RESEARCH
(2019)
Article
Multidisciplinary Sciences
Susan Wyllie, Stephen Brand, Michael Thomas, Manu De Rycker, Chun-wa Chung, Imanol Pena, Ryan P. Bingham, Juan A. Bueren-Calabuig, Juan Cantizani, David Cebrian, Peter D. Craggs, Liam Ferguson, Panchali Goswami, Judith Hobrath, Jonathan Howe, Laura Jeacock, Eun-Jung Ko, Justyna Korczynska, Lorna MacLean, Sujatha Manthri, Maria S. Martinez, Lydia Mata-Cantero, Sonia Moniz, Andrea Nuhs, Maria Osuna-Cabello, Erika Pinto, Jennifer Riley, Sharon Robinson, Paul Rowland, Frederick R. C. Simeons, Yoko Shishikura, Daniel Spinks, Laste Stojanovski, John Thomas, Stephen Thompson, Elisabet Viayna Gaza, Richard J. Wall, Fabio Zuccotto, David Horn, Michael A. J. Ferguson, Alan H. Fairlamb, Jose M. Fiandor, Julio Martin, David W. Gray, Timothy J. Miles, Ian H. Gilbert, Kevin D. Read, Maria Marco, Paul G. Wyatt
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2019)
Article
Microbiology
Clare F. Collett, Carl Kitson, Nicola Baker, Heather B. Steele-Stallard, Marie-Victoire Santrot, Sebastian Hutchinson, David Horn, Sam Alsford
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2019)
Article
Biochemistry & Molecular Biology
Martin Zoltner, Gustavo D. Campagnaro, Gergana Taleva, Alana Burrell, Michela Cerone, Ka-Fai Leung, Fiona Achcar, David Horn, Sue Vaughan, Catarina Gadelha, Alena Zikova, Michael P. Barrett, Harry P. de Koning, Mark C. Field
JOURNAL OF BIOLOGICAL CHEMISTRY
(2020)
Article
Microbiology
Joana Faria, Vanessa Luzak, Laura S. M. Muller, Benedikt G. Brink, Sebastian Hutchinson, Lucy Glover, David Horn, T. Nicolai Siegel
Summary: The study reveals a mechanism in Trypanosoma brucei where a single expressed antigen-coding gene interacts with a major messenger RNA splicing locus in a specific nuclear compartment, ensuring monogenic expression. Specific proteins VEX1 and VEX2 are associated with an antigen exclusion complex, playing a role in this process of antigen transcription and mRNA splicing. Depletion of VEX2 results in loss of monogenic antigen expression and increased interactions between previously silent antigen genes and the splicing locus.
NATURE MICROBIOLOGY
(2021)
Review
Parasitology
David Horn
Summary: Genome-scale genetic screens have played a crucial role in African trypanosomes by uncovering mechanisms related to drug resistance, metabolism, and gene expression control. They have also been effective in identifying potential antitrypanosomal drug targets.
TRENDS IN PARASITOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Simone Altmann, Eva Rico, Sandra Carvalho, Melanie Ridgway, Anna Trenaman, Hannah Donnelly, Michele Tinti, Susan Wyllie, David Horn
Summary: This study reports a simple method for rapid and precise editing of priority drug targets in trypanosomatids. By targeting and editing drug targets, combined with sequencing technology, potential impacts on drug efficacy can be assessed quickly.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Microbiology
Gustavo Bravo Ruiz, Michele Tinti, Melanie Ridgway, David Horn
Summary: VSG expression plays a crucial role in parasite virulence and is a fascinating subject in extreme biology. This study identified three candidate VSG regulators and demonstrated the role of CFB2 in controlling VSG expression through the VSG 3' UTR. Additionally, insights into the connections between VSG expression control, ribosomal protein expression, and cytokinesis were revealed.
Correction
Microbiology
Manu De Rycker, Susan Wyllie, David Horn, Kevin D. Read, Ian H. Gilbert
NATURE REVIEWS MICROBIOLOGY
(2022)
Review
Microbiology
Manu De Rycker, Susan Wyllie, David Horn, Kevin D. Read, Ian H. Gilbert
Summary: Leishmaniasis, Chagas disease, and human African trypanosomiasis are major causes of death and illness, particularly in low- and middle-income countries. The development of new medicines for leishmaniasis and Chagas disease is urgently needed, with limited progress in the clinical pipeline for Chagas disease. This review provides an overview of recent advances in understanding the biology of these pathogens, with a focus on drug discovery, as well as the development of new drug candidates and potential solutions to overcome challenges in clinical development.
NATURE REVIEWS MICROBIOLOGY
(2023)
Article
Multidisciplinary Sciences
Catarina A. Marques, Melanie Ridgway, Michele Tinti, Andrew Cassidy, David Horn
Summary: In this study, a genome-wide RNA-interference library screen was used to investigate the cell cycle defects in Trypanosoma brucei. The results provide comprehensive functional genomic evidence for the known and novel machineries, pathways, and regulators that coordinate trypanosome cell cycle progression.
NATURE COMMUNICATIONS
(2022)
Article
Microbiology
Douglas Escrivani, Viktor Scheidt, Michele Tinti, Joana Faria, David Horn
Summary: Some pathogens use antigenic variation to evade mammalian host adaptive immune responses. African trypanosomes employ variant surface glycoproteins (VSGs) to continually switch their active VSGs and avoid immune recognition. Switched trypanosomes compete in a predictable manner that is dependent on the activated VSG, and the population of cells that activates minichromosome derived VSGs has a competitive advantage.
Article
Microbiology
Anna Trenaman, Michele Tinti, Abdelmadjid Atrih, David Horn
Summary: Nucleoside analogs are widely used as anti-infective agents, but their potential as anti-parasitic agents has not been fully explored. This study identified two proteins, Tb927.6.2800 and HD82, associated with purine analog resistance in African trypanosomes. The findings also validated two nucleoside kinases involved in pro-drug activation. HD82, related to the mammalian nuclear viral restriction factor SAMHD1, sensitized trypanosomes to nucleoside analogs by reducing native nucleotide pools. This study provides insights into nucleoside/nucleotide metabolism and nucleoside analog resistance in trypanosomatids.
Review
Microbiology
Manu De Rycker, Susan Wyllie, David Horn, Kevin D. Read, Ian H. Gilbert
Summary: Leishmaniasis, Chagas disease, and human African trypanosomiasis are causing significant death and morbidity, especially in low- and middle-income countries. There is a critical need for new medications for leishmaniasis and Chagas disease, while the clinical development pipeline for Chagas disease remains sparse. This review discusses recent advancements in understanding the biology of these pathogens, with a focus on drug discovery, and explores progress in developing new drug candidates and identifying potential molecular targets. The challenges in developing new clinical candidates are also discussed, along with potential solutions to overcome these hurdles.
NATURE REVIEWS MICROBIOLOGY
(2023)