Article
Microbiology
Emilia Jane McLaughlin, Karinna Rubio-Pena, Annick Dujeancourt-Henry, Lucy Glover
Summary: This study aimed to disrupt monoallelic VSG expression and found that the DNA sequence of the ectopic VSG is lost in a transcription-dependent manner following DSB-triggered VSG switching. The loss of the ectopic VSG does not disrupt the number or variety of templates used for BES DSB repair, revealing strict mechanisms within the cell to reinforce monoallelic expression during antigenic variation.
Review
Microbiology
Bibo Li, Yanxiang Zhao
Summary: Trypanosoma brucei regularly switches its major surface antigen to evade host immune response, with telomere and subtelomere structure integrity being crucial for its survival and pathogenesis. Telomere proteins TRF and RAP1, with unique nucleic acid binding activities, play key roles in VSG expression and switching. Targeting TbTRF and TbRAP1's nucleic acid binding activities may serve as a potential therapeutic strategy against T. brucei.
Article
Biochemistry & Molecular Biology
Ann-Kathrin Mehnert, Marco Prorocic, Annick Dujeancourt-Henry, Sebastian Hutchinson, Richard McCulloch, Lucy Glover
Summary: In Trypanosoma brucei, RAD50 and MRE11 are essential for RAD51-dependent homologous recombination and phosphorylation of histone H2A following a DNA double strand break. RAD50 suppresses DSB repair using short stretches of homology at a subtelomeric locus, while MRE11 directs DSB resection at the same locus. Loss of either MRE11 or RAD50 leads to increased diversity of expressed VSG variants following DSB repair, suggesting that MRN promotes stringent homologous recombination at subtelomeric loci and restrains antigenic variation.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Immunology
David R. Allred
Summary: Apicomplexan parasites have evolved mechanisms, such as co-opting DNA repair mechanisms, to enhance their survival in hostile environments. This article presents an alternative perspective on the purpose of variant proteins that mediate cytoadhesion, suggesting that it is related to the survival of the oxidative environment. The integration of DNA repair, antigenic variation, and cytoadhesion is influenced by genome organization and has implications for parasite control strategies.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Article
Entomology
Zhiyuan Yang, Mai Shi, Xiaoli Zhang, Danyu Yao
Summary: This study dissected the genomic and transcriptomic profiles of T. brucei, identifying a panel of pathogenic proteins and microRNAs. The findings contribute to a better understanding of the parasite-host interaction mechanisms and provide new insights for designing preventive and therapeutic strategies for African trypanosomiasis.
Article
Multidisciplinary Sciences
Albano H. H. Tenaglia, Lucas A. Lujan, Diego N. N. Rios, Cecilia R. R. Molina, Victor Midlej, Paula A. A. Iribarren, Maria A. Berazategui, Alessandro Torri, Alicia Saura, Damian O. Peralta, Macarena Rodriguez-Walker, Elmer A. A. Fernandez, Juan P. P. Petiti, Marianela C. C. Serradell, Pablo R. R. Gargantini, Tim Sparwasser, Vanina E. E. Alvarez, Wanderley de Souza, Hugo D. D. Lujan
Summary: The genomes of protozoa often contain families of variant surface antigens, and it is believed that antigenic variation in protozoan parasites occurs through the appearance of cells expressing antigenic variants. However, this study shows that antibodies to Variant-specific Surface Proteins (VSPs) of Giardia lamblia do not have cytotoxic effects, but instead induce clustering of VSPs and the release of microvesicles carrying the original VSPs. This mechanism not only challenges current understanding of antigenic switching, but also provides a new framework for understanding host-parasite interactions in protozoan infections.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
John J. Skoko, Juxiang Cao, David Gaboriau, Myriam Attar, Alparslan Asan, Lisa Hong, Candice E. Paulsen, Hongqiang Ma, Yang Liu, Hanzhi Wu, Trey Harkness, Cristina M. Furdui, Yefim Manevich, Ciaran G. Morrison, Erika T. Brown, Daniel Normolle, Maria Spies, Michael Ashley Spies, Kate Carroll, Carola A. Neumann
Summary: This study identifies RAD51 Cys319 as a functionally significant site for the redox regulation of homologous recombination (HR) and cellular responses to ionizing radiation (IR). The loss of peroxiredoxin 1 (PRDX1) inhibits RAD51 focus formation and HR DNA repair, leading to increased DNA damage and sensitization of cells to irradiation.
Article
Plant Sciences
Seobin Yoon, Bum-Kyu Lee, Keun Pil Kim
Summary: The study found that caffeine can enhance the sensitivity of colorectal cancer cells to irinotecan, inhibit cell proliferation, induce cell death, and hinder DNA repair and cell cycle progression. This combination treatment resulted in more severe effects, including DNA fragmentation and mitotic catastrophe.
Article
Oncology
Leonie Schurmann, Lena Schumacher, Katharina Roquette, Anamaria Brozovic, Gerhard Fritz
Summary: The RAD51 inhibitor B02 synergistically increases Doxo-induced cytotoxicity through various mechanisms, including G2/M arrest, mitochondrial damage, and caspase-driven apoptosis. B02 also promotes the cytotoxicity of oxaliplatin and 5-FU, and enhances Doxo-induced cytotoxicity in MMR-proficient colon and mammary carcinoma cells. Pharmacological inhibition of RAD51 is suggested to enhance the cytotoxic effectiveness of conventional anticancer drugs in different tumor entities.
Article
Multidisciplinary Sciences
Jason C. Bell, Christopher C. Dombrowski, Jody L. Plank, Ryan B. Jensen, Stephen C. Kowalczykowski
Summary: Mutations in the BRCA2 gene increase the risk of breast and ovarian cancers. This study shows that BRCA2 accelerates the formation of the RAD51 nucleoprotein filament, which plays a crucial role in DNA repair. BRCA2 also eliminates the kinetic barrier imposed by replication protein-A (RPA), allowing efficient and regulated recombination.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Review
Microbiology
Mohamad S. Hakim, Luthvia Annisa, Rizka O. A. Jariah, Cornelis Vink
Summary: Mycoplasma pneumoniae and Mycoplasma genitalium are important causative agents of infections in humans, with genomes smaller than other prokaryotes and compact DNA recombination and repair-associated genes. These organisms generate antigenic variation through homologous recombination and likely have strategies to maintain the stability of their genomes. Previous studies have shown differences in the DNA recombination and repair machinery of mycoplasmas compared to other bacteria, but the complete activities of the enzymes encoded by Mycoplasma species are not fully understood. Characterizing these proteins may help define the minimal enzymatic requirements for creating bacterial genetic diversity while preserving genomic integrity.
ARCHIVES OF MICROBIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Jin Wook Kang, Zhiyan Zhan, Guangzhen Ji, Youzhou Sang, Daohong Zhou, Yanxin Li, Haizhong Feng, Tao Cheng
Summary: PUMA plays a novel role in regulating DNA repair in stem and progenitor cells by inhibiting double-strand break repair, which provides a new rationale for therapeutic targeting of PUMA.
SIGNAL TRANSDUCTION AND TARGETED THERAPY
(2021)
Article
Oncology
Monica Ganzinelli, Federica Guffanti, Anna Ianza, Navid Sobhani, Sergio Crovella, Fabrizio Zanconati, Cristina Bottin, Marco Confalonieri, Stefano Fumagalli, Alessandra Guglielmi, Daniele Generali, Giovanna Damia
Summary: The study analyzed the correlation between DNA repair biomarkers and survival in malignant pleural mesothelioma (MPM) patients and found that down-regulation of DNA repair expression score is associated with longer survival. These findings could potentially lead to the development of a simple, cost-effective test for better management of MPM patients.
Article
Biology
Judit Jimenez-Sainz, Joshua Mathew, Gemma Moore, Sudipta Lahiri, Jennifer Garbarino, Joseph P. Eder, Eli Rothenberg, Ryan B. Jensen
Summary: This study identified three BRCA2 VUS located in the BRC repeat region and investigated their impact on genome stability. The S1221P and T1980I mutations were found to compromise the cellular response to chemotherapeutics and ionizing radiation, and showed deficits in fork protection. The T1346I mutation, on the other hand, was fully functional. The correct classification of BRCA2 VUS is important as pathogenic variants can impact cancer risk and guide therapy selection during cancer treatment.
Article
Multidisciplinary Sciences
Camila Silva Goncalves, Carolina Moura Costa Catta-Preta, Bruno Repoles, Jeremy C. Mottram, Wanderley De Souza, Carlos Renato Machado, Maria Cristina M. Motta
Summary: Angomonas deanei coevolves in a mutualistic relationship with a symbiotic bacterium that divides in synchronicity with other host cell structures. The deletion of the KAP4 gene affects kDNA arrangement and replication, as well as the maintenance of symbiosis. Mutants lacking KAP4 show atypical phenotypes but are not more sensitive to DNA damage and repair, indicating unique repair mechanisms for kDNA in trypanosomatids.
SCIENTIFIC REPORTS
(2021)
Article
Multidisciplinary Sciences
Nicola Baker, Graham Hamilton, Jonathan M. Wilkes, Sebastian Hutchinson, Michael P. Barrett, David Horn
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2015)
Article
Biology
Yong H. Woo, Hifzur Ansari, Thomas D. Otto, Christen M. Klinger, Martin Kolisko, Jan Michalek, Alka Saxena, Dhanasekaran Shanmugam, Annageldi Tayyrov, Alaguraj Veluchamy, Shahjahan Ali, Axel Bernal, Javier del Campo, Jaromir Cihlar, Pavel Flegontov, Sebastian G. Gornik, Eva Hajduskova, Ales Horak, Jan Janouskovec, Nicholas J. Katris, Fred D. Mast, Diego Miranda-Saavedra, Tobias Mourier, Raeece Naeem, Mridul Nair, Aswini K. Panigrahi, Neil D. Rawlings, Eriko Padron-Regalado, Abhinay Ramaprasad, Nadira Samad, Ales Tomcala, Jon Wilkes, Daniel E. Neafsey, Christian Doerig, Chris Bowler, Patrick J. Keeling, David S. Roos, Joel B. Dacks, Thomas J. Templeton, Ross F. Waller, Julius Lukes, Miroslav Obornik, Arnab Pain
Article
Biochemistry & Molecular Biology
Jaspreet S. Grewal, Karen McLuskey, Debanu Das, Elmarie Myburgh, Jonathan Wilkes, Elaine Brown, Leandro Lemgruber, Matthew K. Gould, Richard J. Burchmore, Graham H. Coombs, Achim Schnaufer, Jeremy C. Mottram
JOURNAL OF BIOLOGICAL CHEMISTRY
(2016)
Article
Evolutionary Biology
Bart Cuypers, Frederik Van den Broeck, Nick Van Reet, Conor J. Meehan, Julien Cauchard, Jonathan M. Wilkes, Filip Claes, Bruno Goddeeris, Hadush Birhanu, Jean-Claude Dujardin, Kris Laukens, Philippe Buscher, Stijn Deborggraeve
GENOME BIOLOGY AND EVOLUTION
(2017)
Article
Multidisciplinary Sciences
Fernando Fernandez-Cortes, Tiago D. Serafim, Jonathan M. Wilkes, Nathaniel G. Jones, Ryan Ritchie, Richard McCulloch, Jeremy C. Mottram
SCIENTIFIC REPORTS
(2017)
Article
Microbiology
Jennifer A. Stortz, Tiago D. Serafim, Sam Alsford, Jonathan Wilkes, Fernando Fernandez-Cortes, Graham Hamilton, Emma Briggs, Leandro Lemgruber, David Horn, Jeremy C. Mottram, Richard McCulloch
Article
Biochemistry & Molecular Biology
Matthew B. Rogers, James D. Hilley, Nicholas J. Dickens, Jon Wilkes, Paul A. Bates, Daniel P. Depledge, David Harris, Yerim Her, Pawel Herzyk, Hideo Imamura, Thomas D. Otto, Mandy Sanders, Kathy Seeger, Jean-Claude Dujardin, Matthew Berriman, Deborah F. Smith, Christiane Hertz-Fowler, Jeremy C. Mottram
Article
Microbiology
Abdirahman I. Abdi, Teresa G. Carvalho, Jonathan M. Wilkes, Christian Doerig
Article
Microbiology
Katrin Kremer, Dirk Kamin, Eva Rittweger, Jonathan Wilkes, Halley Flammer, Sabine Mahler, Joanne Heng, Christopher J. Tonkin, Gordon Langsley, Stefan W. Hell, Vernon B. Carruthers, David J. P. Ferguson, Markus Meissner
Article
Biochemistry & Molecular Biology
Emma Briggs, Graham Hamilton, Kathryn Crouch, Craig Lapsley, Richard McCulloch
NUCLEIC ACIDS RESEARCH
(2018)
Article
Genetics & Heredity
Emma Briggs, Kathryn Crouch, Leandro Lemgruber, Craig Lapsley, Richard McCulloch
Article
Biology
Johannes Felix Stortz, Mario Del Rosario, Mirko Singer, Jonathan M. Wilkes, Markus Meissner, Sujaan Das
Article
Biochemistry & Molecular Biology
Andrea Zurita Leal, Marie Schwebs, Emma Briggs, Nadine Weisert, Helena Reis, Leandro Lemgruber, Katarina Luko, Jonathan Wilkes, Falk Butter, Richard McCulloch, Christian J. Janzen
NUCLEIC ACIDS RESEARCH
(2020)
Article
Microbiology
Federica Giordani, Daniel Paape, Isabel M. Vincent, Andrew W. Pountain, Fernando Fernandez-Cortes, Eva Rico, Ning Zhang, Liam J. Morrison, Yvonne Freund, Michael J. Witty, Rosemary Peter, Darren Y. Edwards, Jonathan M. Wilkes, Justin J. J. van der Hooft, Clement Regnault, Kevin D. Read, David Horn, Mark C. Field, Michael P. Barrett