Article
Chemistry, Multidisciplinary
Sneh M. Toprani, Dimitrios Bitounis, Qiansheng Huang, Nathalia Oliveira, Kee Woei Ng, Chor Yong Tay, Zachary D. Nagel, Philip Demokritou
Summary: The potential genotoxic effects of engineered nanomaterials (ENMs) on DNA repair pathways have been investigated using a fluorescence multiplex-host-cell reactivation (FM-HCR) assay. Results showed that some ENMs may enhance DNA repair capacity while others suppress it. This method can be a valuable part of a multitier, in vitro hazard assessment of ENMs, providing insights into the interplay between ENM properties, DNA repair efficiency, and genomic stability.
Article
Biophysics
Wenjing Liu, Ruqun Wu, Jinlong Guo, Cheng Shen, Jing Zhao, Guangbo Mao, Hongjin Mou, Lei Zhang, Guanghua Du
Summary: The DNA damage response is a highly organized process in which the involvement of DNA damage response factors depends on their biochemical reactions with each other and chromatin. Through live-cell imaging combined with heavy ion microbeam irradiation, this study investigated the response of XRCC1 in localized DNA damage and found that its recruitment and dissociation dynamics differed between the G1 and G2 phase. Furthermore, fractionated irradiation led to accelerated dissociation at previous damage sites and immediate recycling of XRCC1 with higher recruitment efficiency.
BIOPHYSICAL JOURNAL
(2022)
Review
Biochemistry & Molecular Biology
Dana Jurkovicova, Christiana M. Neophytou, Ana Cipak Gasparovic, Ana Cristina Goncalves
Summary: Resistance to chemo- and radiotherapy is a common occurrence in cancer patients, necessitating the continuous investigation and development of new cancer therapies. The DNA damage response (DDR) plays a crucial role in maintaining genomic stability, but defects in DDR machinery are associated with different types of cancers. Current developments include the use of poly (ADP-ribose) polymerase inhibitors (PARP inhibitors) as DDR inhibitors (DDRi) for various cancers. However, resistance to DDRi, including PARP inhibitors, is becoming a growing concern in clinical settings. This review highlights the importance of DDR pathways in cancer therapy, its role in treatment resistance, and its potential for anticancer treatment.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Obstetrics & Gynecology
Kashmira Bane, Junita Desouza, Diksha Shetty, Prakash Choudhary, Shalaka Kadam, R. R. Katkam, Gwendolyn Fernandes, Raj Sawant, Uddhavraj Dudhedia, Neeta Warty, Anahita Chauhan, Uddhav Chaudhari, Rahul Gajbhiye, Geetanjali Sachdeva
Summary: The study indicates that the DNA damage response is dysregulated in the eutopic endometrium of women with endometriosis, with higher expression of DDR genes compared to those without the disease. Additionally, DNA repair genes are also up-regulated in the eutopic endometrium of women with endometriosis.
HUMAN REPRODUCTION
(2021)
Review
Oncology
Cole Petrilla, Joshua Galloway, Ruchi Kudalkar, Aya Ismael, Francesca Cottini
Summary: Multiple myeloma (MM) is a plasma cell malignancy characterized by genetic abnormalities that affect the DNA damage response (DDR) and DNA repair mechanisms. The altered DDR in MM promotes tumor development, progression, and resistance to therapies. Treatments used for MM patients can induce DNA damage, highlighting the potential for targeting DDR mechanisms as new therapeutic opportunities.
Review
Biochemistry & Molecular Biology
Mi Ae Kang, Jong-Soo Lee
Summary: CTCF, a highly conserved multifunctional DNA-binding protein with 11 zinc fingers, plays crucial roles in diverse genomic processes such as transcriptional regulation, insulation, genome imprinting, and maintenance of genome organization. Recent findings reveal that CTCF is involved in DNA double-strand break (DSB) repair through homologous recombination (HR), facilitating accurate restoration of broken DNA sequences. Understanding the functional crosstalks between CTCF and other HR factors may shed light on the molecular basis of various human diseases and the diverse functions of CTCF in genome biology.
Review
Genetics & Heredity
Yongxin Li, Yan Tong, Jiaqi Liu, Jianlin Lou
Summary: DNA is crucial for organism development and function. MiRNA, a type of non-coding RNA, may play an important role in the DNA damage response by influencing processes like cell cycle, DNA repair, and apoptosis, thereby impacting genomic stability and tumorigenesis.
FRONTIERS IN GENETICS
(2022)
Article
Biochemistry & Molecular Biology
Mahsa Karbaschi, Yunhee Ji, Mubarak A. Mujawar, Mario Mendoza, Juan S. Marquez, Apurva Sonawane, Pratikkumar Shah, Chris Ross, Shekhar Bhansali, Marcus S. Cooke
Summary: This article describes the development of an automated device for high throughput sample processing in a comet assay, which reliably assesses DNA damage in individual eukaryotic cells. The device performs as well as manual methods but with the advantages of decreased human involvement and assay run time, making it a valuable approach for high throughput DNA damage assessment.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Oncology
Caroline Molinaro, Alain Martoriati, Katia Cailliau
Summary: Cells respond to genotoxic stress through complex protein pathways called DNA damage response (DDR), ensuring genomic integrity and activating processes like DNA repair, cell cycle regulation, and programmed cell death. Alterations in DDR network proteins can lead to various diseases, including cancer. Recent technological advancements have allowed for the exploitation of DDR vulnerabilities to improve cancer treatments through DNA damage strategies and combination therapies.
Article
Oncology
Sweta Sharma Saha, Lucy Gentles, Alice Bradbury, Dominik Brecht, Rebecca Robinson, Rachel O'Donnell, Nicola J. Curtin, Yvette Drew
Summary: This study identified that genomic/transcriptomic and/or functional alterations in DDR pathways can determine therapy response, offering insights into personalized chemotherapy choices for ovarian cancer patients.
Article
Biochemistry & Molecular Biology
Hadar Golan Berman, Pooja Chauhan, Shira Shalev, Hiba Hassanain, Avital Parnas, Sheera Adar
Summary: The study identified that in a specific cell line system, cisplatin resistant cells had less damage but similar repair kinetics. Through mapping gene expression changes, 56 upregulated genes were identified that could potentially impact the response to cisplatin.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Engineering, Biomedical
Yuki Ichioka, Farah Asa'ad, Behnosh Ohrnell Malekzadeh, Anna Westerlund, Lena Larsson
Summary: The study found that the surface characteristics of minimally rough titanium do impact DNA damage and repair pathways, including epigenetic factors. Compared to smooth titanium, minimally rough titanium surfaces induce less DNA damage and higher levels of DNA repair cells.
JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A
(2021)
Article
Oncology
Kimiko L. Krieger, Jie H. Gohlke, Kevin J. Lee, Danthasinghe Waduge Badrajee Piyarathna, Patricia D. Castro, Jeffrey A. Jones, Michael M. Ittmann, Natalie R. Gassman, Arun Sreekumar
Summary: This study found that prostate cancer in African American patients has more severe DNA damage, indicating dysfunction in the base excision repair pathway and metabolic rewiring, which can explain the poorer outcomes in African American men compared to European American men with prostate cancer.
Article
Biochemistry & Molecular Biology
Le P. Ngo, Simran Kaushal, A. Isaac Chaim, Patrizia Mazzucato, Catherine Ricciardi, D. Leona Samson, D. Zachary Nagel, P. Bevin Engelward
Summary: By utilizing the CometChip, researchers uncovered significant variability in DNA repair efficiency among individuals, indicating its potential utility in future epidemiological and clinical studies.
FREE RADICAL BIOLOGY AND MEDICINE
(2021)
Article
Cell Biology
Audrey Chansard, Enrico Pobega, Pierre Caron, Sophie E. Polo
Summary: The organization of chromatin has a significant impact on DNA damage repair. Heterochromatin, through transcriptional silencing, plays a vital role in maintaining genome integrity and cellular homeostasis. Understanding the effect of heterochromatin on the DNA damage response is critical, and this study presents two laser micro-irradiation-based methods for imaging the DDR in heterochromatin domains in mammalian cells.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Cell Biology
Michel Owusu, Peter Bannauer, Joana Ferreira da Silva, Thanos P. Mourikis, Alistair Jones, Peter Majek, Michael Caldera, Marc Wiedner, Charles-Hugues Lardeau, Andre C. Mueller, Joerg Menche, Stefan Kubicek, Francesca D. Ciccarelli, Joanna I. Loizou
Article
Multidisciplinary Sciences
Katrin Unterhauser, Lisa Poeltl, Georg Schneditz, Sabine Kienesberger, Ronald A. Glabonjat, Maksym Kitsera, Jakob Pletz, Fernando Josa-Prado, Elisabeth Dornisch, Christian Lembacher-Fadum, Sandro Roier, Gregor Gorkiewicz, Daniel Lucena, Isabel Barasoain, Wolfgang Kroutil, Marc Wiedner, Joanna I. Loizou, Rolf Breinbauer, Jose Fernando Diaz, Stefan Schild, Christoph Hoegenauer, Ellen L. Zechner
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2019)
Article
Hematology
Barbara Maurer, Harini Nivarthi, Bettina Wingelhofer, Ha Thi Thanh Pham, Michaela Schlederer, Tobias Suske, Reinhard Grausenburger, Ana-Iris Schiefer, Michaela Prchal-Murphy, Doris Chen, Susanne Winkler, Olaf Merkel, Christoph Kornauth, Maximilian Hofbauer, Birgit Hochgatterer, Gregor Hoermann, Andrea Hoelbl-Kovacic, Jana Prochazkova, Cosimo Lobello, Abbarna A. Cumaraswamy, Johanna Latzka, Melitta Kitzwoegerer, Andreas Chott, Andrea Janikova, Sarka Pospisilova, Joanna Loizou, Stefan Kubicek, Peter Valent, Thomas Kolbe, Florian Grebien, Lukas Kenner, Patrick T. Gunning, Robert Kralovics, Marco Herling, Mathias Mueller, Thomas Ruelicke, Veronika Sexl, Richard Moriggl
Article
Medicine, Research & Experimental
Cecilia Dominguez Conde, Oezlem Yuece Petronczki, Safa Baris, Katharina L. Willmann, Enrico Girardi, Elisabeth Salzer, Stefan Weitzer, Rico Chandra Ardy, Ana Krolo, Hanna Ijspeert, Ayca Kiykim, Elif Karakoc-Aydiner, Elisabeth Forster-Waldl, Leo Kager, Winfried F. Pickl, Giulio Superti-Furga, Javier Martinez, Joanna Loizou, Ahmet Ozen, Mirjam van der Burg, Kaan Boztug
JOURNAL OF CLINICAL INVESTIGATION
(2019)
Article
Multidisciplinary Sciences
Joana Ferreira da Silva, Sejla Salic, Marc Wiedner, Paul Datlinger, Patrick Essletzbichler, Alexander Hanzl, Giulio Superti-Furga, Christoph Bock, Georg Winter, Joanna I. Loizou
SCIENTIFIC REPORTS
(2019)
Article
Oncology
Jaqueline Ramalho Buttura, Monize Nakamoto Provisor Santos, Renan Valieris, Rodrigo Duarte Drummond, Alexandre Defelicibus, Joao Paulo Lima, Vinicius Fernando Calsavara, Helano Carioca Freitas, Vladmir C. Cordeiro de Lima, Thais Fernanda Bartelli, Marc Wiedner, Rafael Rosales, Kenneth John Gollob, Joanna Loizou, Emmanuel Dias-Neto, Diana Noronha Nunes, Israel Tojal da Silva
Summary: This study identified three mutational signatures related to DNA mismatch repair deficiency (dMMR) in gastric cancer, one of which can accurately discriminate tumors with MLH1 gene silencing caused by promoter hypermethylation. Classification based on mutational signature exposure can help identify patients with better prognosis in gastric cancer.
Article
Biochemistry & Molecular Biology
Katja Kratz, Mariela Artola-Boran, Saho Kobayashi-Era, Gene Koh, Goncalo Oliveira, Shunsuke Kobayashi, Andreia Oliveira, Xueqing Zou, Julia Richter, Masataka Tsuda, Hiroyuki Sasanuma, Shunichi Takeda, Joanna Loizou, Alessandro A. Sartori, Serena Nik-Zainal, Josef Jiricny
Summary: A study revealed a new exonuclease, FAN1, which can efficiently substitute for EXO1 in the mismatch repair process, with its functional complementation modulated by its interaction with MLH1. Loss of FAN1 exacerbates the mutational profile of EXO1-deficient cells, suggesting redundant action of these two nucleases in the same antimutagenic pathway.
MOLECULAR AND CELLULAR BIOLOGY
(2021)
Article
Oncology
Ruochen Jia, Leon Kutzner, Anna Koren, Kathrin Runggatscher, Peter Majek, Andre C. Mueller, Michael Schuster, Christoph Bock, Joanna I. Loizou, Stefan Kubicek, Robert Kralovics
Summary: Mutations of calreticulin (CALR) are the second most common driver mutations in essential thrombocythemia and primary myelofibrosis. A study identified synthetic lethality with compounds targeting the ATR-CHK1 pathway in CALR mutated cells, highlighting the potential therapeutic target in CALR mutated hematopoietic cells. CHK1 inhibitors induced replication stress and S-phase cell cycle arrest in CALR mutated cells, demonstrating specificity for the oncogenic activation by the mutant CALR.
BLOOD CANCER JOURNAL
(2021)
Article
Multidisciplinary Sciences
J. Ferreira da Silva, G. P. Oliveira, E. A. Arasa-Verge, C. Kagiou, A. Moretton, G. Timelthaler, J. Jiricny, J. Loizou
Summary: Prime editing is a powerful genome engineering approach that can introduce various modifications into the genome. This study identifies the mismatch repair pathway as inhibitory for Prime editing, and loss of mismatch repair enhances its efficiency.
NATURE COMMUNICATIONS
(2022)
Article
Oncology
Amandine Moretton, Jana Slyskova, Marwan E. Simaan, Emili A. Arasa-Verge, Mathilde Meyenberg, D. Alonso Cerron-Infantes, Miriam M. Unterlass, Joanna I. Loizou
Summary: In this study, a series of cisplatin derivatives compatible with click chemistry were synthesized to investigate the repair of DNA crosslinks and cellular responses. It was found that these compounds bind to DNA and generate DNA damage. They can be visualized and quantified in cells through fluorescence probes and biotin tagging, respectively. Furthermore, one of the compounds can be used to identify DNA repair proteins.
FRONTIERS IN ONCOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Amandine Moretton, Savvas Kourtis, Antoni Ganez Zapater, Chiara Calabro, Maria Lorena Espinar Calvo, Frederic Fontaine, Evangelia Darai, Etna Abad Cortel, Samuel Block, Laura Pascual-Reguant, Natalia Pardo-Lorente, Ritobrata Ghose, Matthew G. Vander Heiden, Ana Janic, Andre C. Mueller, Joanna Loizou, Sara Sdelci
Summary: This study investigates the role of cellular metabolism in DNA damage repair and identifies Peroxiredoxin 1 (PRDX1) as a contributor to this process. By integrating functional genomics with chromatin proteomics and metabolomics, the interplay between cellular metabolism and the DNA damage response is elucidated.
MOLECULAR SYSTEMS BIOLOGY
(2023)
Article
Cell Biology
Louis Debar, Layal Ishak, Amandine Moretton, Saber Anoosheh, Frederic Morel, Louise Jenninger, Isabelle Garreau-Balandier, Patrick Vernet, Anders Hofer, Siet Van den Wildenberg, Geraldine Farge
Summary: The NUDIX hydrolase superfamily consisting of 22 members can hydrolyze various phosphorylated molecules. In this study, NUDT6 and NUDT9 were found to play roles in mitochondria, and their deficiency led to increased respiratory chain activity and altered expression of mitochondrial respiratory chain complexes. Furthermore, NUDT6 showed higher activity towards NADH, while NUDT9 displayed higher activity towards ADPR.
Review
Oncology
Anna Schrempf, Jana Slyskova, Joanna Loizou
Summary: Targeted cancer therapies focusing on POLQ, an error-prone translesion polymerase involved in DNA repair, represent a promising approach in personalized cancer treatment. Inhibition of POLQ, currently under development, shows potential for more effective cancer therapies in the future.