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
Genetics & Heredity
Jac A. Nickoloff, Neelam Sharma, Lynn Taylor, Sage J. Allen, Robert Hromas
Summary: Cells need to accurately replicate and segregate DNA to prevent cancer, but replication forks can encounter obstacles leading to replication stress. Cells respond by activating DNA damage response pathways to delay cell cycle progression, stimulate repair and replication fork restart, or induce apoptosis. Resection of single-ended double-strand breaks (seDSBs) and accurate fork restart by homologous recombination are crucial in maintaining genome stability.
FRONTIERS IN GENETICS
(2021)
Article
Neurosciences
Xiaoyu Zhang, Yan Liu, Ming Huang, Sumedha Gunewardena, Mohammad Haeri, Russell H. Swerdlow, Ning Wang
Summary: This study identified an accumulation of DNA double-strand breaks (DSBs) in Alzheimer's disease (AD) brains, which differed from the pattern in control brains. The aberrant DSB formation was associated with AD-associated genetic variations, increased chromatin accessibility, and upregulated gene expression.
JOURNAL OF ALZHEIMERS DISEASE
(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)
Review
Biochemistry & Molecular Biology
Jac A. Nickoloff, Aruna S. Jaiswal, Neelam Sharma, Elizabeth A. Williamson, Manh T. Tran, Dominic Arris, Ming Yang, Robert Hromas
Summary: Replicative DNA polymerases are obstructed by various DNA damage, leading to DNA replication stress that threatens genome stability. Cellular responses to replication stress include cell cycle arrest, replication fork collapse, DNA repair induction, and programmed cell death. Nucleases play critical roles in these responses, promoting repair and restart of stressed replication forks. Understanding biological responses to genome-wide replication stress can inform novel cancer treatment strategies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cell Biology
Md Akram Hossain, Yunfeng Lin, Garrett Driscoll, Jia Li, Anne McMahon, Joshua Matos, Haichao Zhao, Daisuke Tsuchimoto, Yusaku Nakabeppu, Jianjun Zhao, Shan Yan
Summary: APE2 is essential for activating the ATR DDR pathway in response to various stressful conditions in Xenopus laevis egg extracts and human pancreatic cancer cells. Inhibition of APE2 leads to increased DNA damage and sensitizes cancer cells to chemotherapy drugs, indicating its crucial role in maintaining genome integrity.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Engineering, Multidisciplinary
Kamila Sofi, Michal Ciesla, Jakub Barbasz, Natalia Wilkosz, Ewelina Lipiec, Marek Szymonski, Piotr Bialas
Summary: DNA is susceptible to various damaging factors, which can cause single- or double-strand breaks. Atomic force microscopy is used to determine the length of DNA fragments deposited on surfaces and quantify double-strand breaks. To overcome the underestimation caused by image resolution, a new methodology based on statistics of DNA fragment length is proposed, along with software for automatic calculation of double-strand breaks. The method is applied to characterize DNA plasmid fragmentation caused by the anticancer chemotherapeutic drug bleomycin.
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
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
Multidisciplinary Sciences
Michael Schmalz, Xiao- Xuan Liang, Ines Wieser, Caroline Gruschel, Lukas Muskalla, Martin Thomas Stoeckl, Roland Nitschke, Norbert Linz, Alfred Leitenstorfer, Alfred Vogel, Elisa Ferrando-May, Wei Yang
Summary: Understanding and predicting the outcome of light-DNA interaction is crucial for DNA repair and radiotherapy. This study combines laser microirradiation, imaging, and modeling to investigate the damage pathways in live cells. The results show that photochemical damage dominates at 515 nm, while electron-mediated damage dominates at wavelengths ≥620 nm. The study provides a conceptual framework for interpreting the wavelength-dependent DNA damage induced by laser and electron interactions.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Biochemistry & Molecular Biology
Genevieve Trombly, Afaf Milad Said, Alexei P. Kudin, Viktoriya Peeva, Janine Altmueller, Kerstin Becker, Karl Koehrer, Gabor Zsurka, Wolfram S. Kunz
Summary: The study investigated the effects of hydrogen peroxide on mitochondrial DNA integrity. The results showed that hydrogen peroxide treatment resulted in DNA breaks, which were then repaired through rapid repair of single-strand breaks and degradation of double-strand breaks-generated linear fragments. Inactivation of mitochondrial DNA degradation resulted in the persistence of linear fragments in mutant cells without affecting the repair of single-strand breaks. These findings highlight the interplay between DNA repair and degradation processes, and the potential generation of somatic mitochondrial DNA deletions.
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
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.
Review
Hematology
Christina-Nefeli Kontandreopoulou, Panagiotis T. Diamantopoulos, Despina Tiblalexi, Nefeli Giannakopoulou, Nora-Athina Viniou
Summary: PARP1 plays a crucial role in DNA damage repair and cancer progression, with its inhibitors showing promise in a wider range of patients. Ongoing clinical trials suggest the potential of PARPis in targeted treatment of various hematologic malignancies, highlighting their effectiveness in overcoming resistance.
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)