Review
Cell Biology
Ksenia G. Kolobynina, Alexander Rapp, M. Cristina Cardoso
Summary: Chromatin serves as the background for all DNA-based molecular processes in the cell nucleus. The initial chromatin structure at the site of DNA damage determines lesion generation and activation of the DNA damage response pathway. Ubiquitination, as an important chromatin post-translational modification, is involved in chromatin changes at the damaged site and throughout the genome.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Review
Cell Biology
Marcelo Santos da Silva
Summary: This article discusses the unique dependence of trypanosomatids on DSBs for important events such as antigenic variation, genetic exchange, and genomic changes, as well as how they balance the benefits and challenges caused by DSBs through homologous recombination.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Ricardo Peraza-Vega, Mahara Valverde, Emilio Rojas
Summary: The repair of DNA damage is crucial for maintaining genetic information and cell functioning. Double-strand breaks (DSBs) are the most harmful type of DNA damage, and their repair involves two main mechanisms: non-homologous end joining (NHEJ) and homologous recombination repair (HRR). MiRNAs have been shown to play an important role in regulating genes involved in NHEJ and HRR, and alterations in miRNA expression can impact the ability of cells to repair DSBs and affect cancer therapy sensitivity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Alejandra Fernandez, Connor O'Leary, Kenneth J. O'Byrne, Joshua Burgess, Derek J. Richard, Amila Suraweera
Summary: Upon DNA damage induction, chromatin unwinds to allow repair enzymes access. Epigenetic modifications regulate this process and inhibitors of histone deacetylases and DNA methyltransferases play crucial roles in repairing double strand breaks, showing promise in cancer therapy.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2021)
Editorial Material
Genetics & Heredity
Juan G. Alvarez, Agustin Garcia-Peiro, Alberto Barros, Luis Ferraz, Mario Sousa, Denny Sakkas
Summary: The purpose of this opinion paper is to explore and enhance our understanding of the quantity of double-strand DNA breaks in sperm and whether there is a threshold beyond which repair becomes impossible. The paper reviews literature on the theories explaining the occurrence of double-strand breaks in human spermatozoa, discusses their detection methods and how oocytes or embryos may handle them, and presents a strategy for dealing with patients with high levels of double-strand DNA breaks in their sperm through testicular sperm extraction.
JOURNAL OF ASSISTED REPRODUCTION AND GENETICS
(2023)
Review
Cell Biology
Zulong Chen, Jessica K. Tyler
Summary: This review presents our current understanding of how DNA double-strand break repair pathways are employed in various chromatin landscapes, with a focus on the impact of histone post-translational modifications and damage-induced chromatin modifications on repair pathway choice. The potential roles of RNA transcripts from DSBs in actively transcribed regions in regulating repair pathway choice are also discussed.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Review
Genetics & Heredity
Apfrida Kendek, Marieke R. Wensveen, Aniek Janssen
Summary: The eukaryotic nucleus is constantly exposed to sources causing DNA breaks, requiring dedicated nuclear machinery for faithful repair. DNA is packaged into various chromatin domains with specific molecular properties regulating gene expression and nuclear structure maintenance. Different chromatin environments demand tailored responses to DNA damage.
Article
Oncology
Qunsong Tan, Kaifeng Niu, Yuqi Zhu, Zixiang Chen, Yueyang Li, Mengge Li, Di Wei, Adayabalam S. Balajee, Hongbo Fang, Yongliang Zhao
Summary: The study demonstrates that RNF8 ubiquitinates RecQL4 protein, facilitating its dissociation from DSB sites and hindering the recruitment of downstream DSB repair proteins. RecQL4 also interacts with WRAP53 beta, which enhances its association with RNF8. Overall, the ubiquitination event mediated by RNF8 is essential for RecQL4's function in DSB repair.
Review
Environmental Sciences
Ericka Marel Quezada-Maldonado, Yesennia Sanchez-Perez, Yolanda I. Chirino, Claudia M. Garcia-Cuellar
Summary: This study analyzed the types of DNA damage and alterations in DNA repair pathways induced by PM exposure, showing that PM mainly causes oxidative stress and DNA damage through the formation of DNA adducts and DSBs, as well as deregulates the protein expression in DNA repair pathways. However, there are still limitations in the knowledge about the effects of PM on DNA repair pathways, and further research is needed to deepen our understanding.
ENVIRONMENTAL POLLUTION
(2021)
Review
Biochemistry & Molecular Biology
Yunhui Li, Jian Yuan
Summary: DNA is the hereditary material in humans and most other organisms, crucial for accurate transmission of genetic information. Damage to DNA, including DSBs, can lead to gene mutations, genome instability, and even tumorigenesis if repair mechanisms are defective. Protein deubiquitination is essential in DNA DSB repair, and understanding the molecular mechanisms of DUB regulation can provide insights for combatting human diseases and developing new therapeutic approaches.
JOURNAL OF ZHEJIANG UNIVERSITY-SCIENCE B
(2021)
Article
Cell Biology
Nathalie Berthault, Ptissam Bergam, Floriane Pereira, Pierre-Marie Girard, Marie Dutreix
Summary: AsiDNA, a DNA repair inhibitor, disrupts DNA double-strand breaks (DSB) repair pathways to sensitize tumors to DNA damaging therapies. It activates ATM and PARP in the cytoplasm, preventing the formation of repair foci on irradiation-induced damage. AsiDNA also associates with DNA-PK in the nucleus to inhibit the recruitment of repair enzymes at damage sites.
Article
Biochemistry & Molecular Biology
Sijie Liu, Yu Hua, Jingna Wang, Lingyan Li, Junjie Yuan, Bo Zhang, Ziyang Wang, Jianguo Ji, Daochun Kong
Summary: Protection of 30 overhangs in DNA double-strand breaks (DSBs) repair is achieved through the transient formation of RNA-DNA hybrids, with RNA polymerase III (RNAPIII) responsible for synthesizing the RNA strand. CtIP and MRN nuclease activity are required for initiating RNAPIII-mediated RNA synthesis at DSBs. Reduced RNAPIII levels suppress homologous recombination (HR) and lead to genetic loss > 30 bp at DSBs.
Article
Biochemistry & Molecular Biology
Philipp Palombo, Alexander Buerkle, Maria Moreno-Villanueva
Summary: In vitro mechanistic research often overlooks the potential influence of cell culture media and supplements, leading to the potential oversight of interactions between compounds and medium ingredients. Isoproterenol, a synthetic catecholamine commonly used in biomedical research, has different stability in different cell culture media. The differences in effective levels of isoproterenol and the formation of oxidation products may explain the discrepancies observed in its genotoxicity and cytotoxicity.
CHEMICO-BIOLOGICAL INTERACTIONS
(2022)
Article
Biochemistry & Molecular Biology
Almudena Serrano-Benitez, Sophie E. Wells, Lylah Drummond-Clarke, Lilian C. Russo, John Christopher Thomas, Giovanna A. Leal, Mark Farrow, James Michael Edgerton, Shankar Balasubramanian, Ming Yang, Christian Frezza, Amit Gautam, Jan Brazina, Kamila Burdova, Nicolas C. Hoch, Stephen P. Jackson, Keith W. Caldecott
Summary: DNA single-strand breaks (SSBs) play a role in disrupting DNA replication and causing chromosome breakage. This study investigates whether SSBs induce chromosome breakage when located behind or ahead of replication forks, and finds that only SSBs ahead of replication forks trigger fork collapse and chromosome breakage. Furthermore, the study shows that CldU, a thymidine analogue, is cytotoxic to cells lacking SSB repair mechanisms and its incorporation in template DNA is particularly harmful during the following cell cycle. Additionally, BRCA-defective cells are highly sensitive to CldU, suggesting its potential clinical utility.
Article
Medicine, Research & Experimental
Grace Oh, Annie Wang, Lidong Wang, Jiufeng Li, Gregor Werba, Daniel Weissinger, Ende Zhao, Surajit Dhara, Rosmel E. Hernandez, Amanda Ackermann, Sarina Porcella, Despoina Kalfakakou, Igor Dolgalev, Emily Kawaler, Talia Golan, Theodore H. Welling, Agnel Sfeir, Diane M. Simeone
Summary: Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy with specific vulnerabilities to certain therapies. Inactivation of the HR pathway and overexpression of POLQ are associated with PDAC. Knockdown of POLQ enhances tumor immune infiltration and can be used as a synthetic lethal approach to inhibit tumor growth.
JOURNAL OF CLINICAL INVESTIGATION
(2023)
Article
Biochemistry & Molecular Biology
Margaux Olivier, Cyril Charbonnel, Simon Amiard, Charles I. White, Maria E. Gallego
NUCLEIC ACIDS RESEARCH
(2018)
Article
Plant Sciences
Takeshi Hirakawa, Keiko Kuwata, Maria E. Gallego, Charles White, Mika Nomoto, Yasuomi Tada, Sachihiro Matsunaga
Article
Plant Sciences
Olivier Da Ines, Robin Michard, Ian Fayos, Giacomo Bastianelli, Alain Nicolas, Emmanuel Guiderdoni, Charles White, Pierre Sourdille
Article
Plant Sciences
Benyahya Fatiha, Nadaud Isabelle, Da Ines Olivier, Rimbert Helene, White Charles, Sourdille Pierre
Article
Genetics & Heredity
Nathalie Grandin, Maria Eugenia Gallego, Charles White, Michel Charbonneau
Article
Genetics & Heredity
Miguel Hernandez Sanchez-Rebato, Alida M. Bouatta, Maria E. Gallego, Charles I. White, Olivier Da Ines
Summary: RAD54 protein plays a crucial role in repairing meiotic double strand breaks by RAD51 in the plant Arabidopsis thaliana, particularly in the absence of DMC1. Its function in meiosis is mainly downstream of the support provided by RAD51 to DMC1 activity. These findings provide new insights into the regulation of homologous recombination in plants.
Article
Biochemistry & Molecular Biology
Ying Huang, Sanchari Sicar, Juan S. Ramirez-Prado, Deborah Manza-Mianza, Javier Antunez-Sanchez, Rim Brik-Chaouche, Natalia Y. Rodriguez-Granados, Jing An, Catherine Bergounioux, Magdy M. Mahfouz, Heribert Hirt, Martin Crespi, Lorenzo Concia, Fredy Barneche, Simon Amiard, Aline Probst, Jose Gutierrez-Marcos, Federico Ariel, Cecile Raynaud, David Latrasse, Moussa Benhamed
Summary: The study reveals the crucial role of H3K27me3 in regulating chromatin interactions in plants, showing that reducing H3K27me3 levels can lead to a global reconfiguration of chromatin architecture and impact gene transcription. These findings highlight the tight link between 3D genome organization and reversible histone modifications in governing chromatin interactions.
Article
Biochemistry & Molecular Biology
Marina Martinez-Garcia, Charles I. White, F. Chris. H. Franklin, Eugenio Sanchez-Moran
Summary: TOPII plays an essential endogenous role in normal root growth, cell cycle regulation, mitotic DNA repair through homologous recombination, and meiotic DNA repair progression in Arabidopsis thaliana. While it is required for meiotic double-strand break repair, it does not affect crossover formation. It is proposed that TOPII may facilitate mitotic homologous recombination DNA repair by relieving stress necessary for strand invasion and D-loop formation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Anis Meschichi, Lihua Zhao, Svenja Reeck, Charles White, Olivier Da Ines, Adrien Sicard, Frederic Pontvianne, Stefanie Rosa
Summary: The study investigated the mobility of chromosomes and double-strand break (DSB) sites in response to DNA damage in Arabidopsis thaliana. The results showed an increase in chromatin mobility, particularly in the S/G2 phases of the cell cycle. This increased mobility was dependent on the DNA damage response transcription factor sog1-1 and the HR factor RAD54, suggesting a role of chromatin mobility in the early steps of the DNA damage response.
Article
Genetics & Heredity
Olivier Da Ines, Jeanne Bazile, Maria E. Gallego, Charles I. White
Summary: Meiotic recombination is essential for fertility in sexually reproducing organisms, and it requires the DNA strand-exchange proteins RAD51 and DMC1 to repair DNA double strand breaks. DMC1 is meiosis-specific and RAD51 is essential for both mitotic and meiotic homologous recombination. In plants, DMC1 is the main active protein involved in meiotic suppression of RAD51, and its downregulation is associated with local assembly of DMC1 at DNA breaks.
Article
Biotechnology & Applied Microbiology
Pierre Bourguet, Leticia Lopez-Gonzalez, Angeles Gomez-Zambrano, Thierry Pelissier, Amy Hesketh, Magdalena E. Potok, Marie-Noelle Pouch-Pelissier, Magali Perez, Olivier Da Ines, David Latrasse, Charles I. White, Steven E. Jacobsen, Moussa Benhamed, Olivier Mathieu