Article
Neurosciences
Semer Maksoud
Summary: Gliomas are the most common tumors in the central nervous system, characterized by cellular infiltration, heterogeneity, and the presence of stem-like cells. These properties make their treatment difficult, especially in response to chemoradiotherapy. This review focuses on DNA double-strand breaks, an important type of genetic material damage, and how gliomas regulate their formation and repair. It discusses the therapeutic potential of inducing these breaks and suppressing their repair as a mechanism to control brain tumor development.
MOLECULAR NEUROBIOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Sayma Zahid, Murielle Seif El Dahan, Florence Iehl, Paloma Fernandez-Varela, Marie-Helene Le Du, Virginie Ropars, Jean Baptiste Charbonnier
Summary: DNA double-strand breaks are accidental lesions caused by various stresses and genetically programmed events. Most DSBs are repaired in mammalian cells through the classical nonhomologous end-joining pathway, with Ku playing a central role. In addition to its DNA repair function, Ku is involved in various other DNA metabolism processes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cell Biology
Jong-Hyuk Lee, Raghavendra A. Shamanna, Tomasz Kulikowicz, Nima Borhan Fakouri, Edward W. Kim, Louise S. Christiansen, Deborah L. Croteau, Vilhelm A. Bohr
Summary: Werner syndrome (WS) is an accelerated aging disorder characterized by genomic instability caused by WRN protein deficiency. The phosphorylation of WRN by CDK2 on serine residue 426 is critical for WRN to choose between non-homologous end joining (NHEJ) and homologous recombination (HR) pathways. The phosphorylation stabilizes WRN's affinity for RPA and enhances its role in long-range resection, a crucial step for HR.
Article
Cell Biology
Anke Geng, Shiya Xu, Yunxia Yao, Zhen Qian, Xiyue Wang, Jiahui Sun, Jingyuan Zhang, Fangfang Shi, Zhixi Chen, Weina Zhang, Zhiyong Mao, Wen Lu, Ying Jiang
Summary: Chrysin impairs genomic stability in breast cancer cells by inhibiting DNA double-strand break repair, which leads to accumulation of DNA damage and enhances sensitivity to chemotherapy. This compound also delays the recruitment of key factors involved in repair mechanisms, proposing a potential curative effect when combined with chemotherapy in breast cancer treatment.
Article
Biochemistry & Molecular Biology
Beomjong Song, Soyeon Yang, Gue-Ho Hwang, Jihyeon Yu, Sangsu Bae
Summary: Genome editing using CRISPR-Cas9 nucleases relies on DNA double-strand break (DSB) repair, with NHEJ pathway being dominant with an average accuracy of around 75% in human cells. Accuracy of NHEJ repair is sequence-dependent, with lower values observed at DSB ends close to protospacer adjacent motif (PAM). Additionally, a negative correlation is found between insertion mutation ratio and NHEJ accuracy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Vincent E. Provasek, Joy Mitra, Vikas H. Malojirao, Muralidhar L. Hegde
Summary: The continuous process of DNA damage and repair is crucial for maintaining genomic integrity. Among different types of DNA damage, double-strand breaks (DSBs) are the most dangerous and require timely repair. DSB repair is particularly important for nondividing, post-mitotic cells in the central nervous system (CNS), as failure in these mechanisms can lead to disruptions in neural networks and motor functions. In addition to repair pathways, DNA damage response (DDR) signaling and hnRNP proteins have been found to play important roles in neuronal DSB repair and are linked to age-associated neurological disorders.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Cell Biology
Huiming Lu, Anthony J. Davis
Summary: RecQ DNA helicases are a conserved protein family found in various organisms, playing important roles in cellular functions and potentially contributing to autosomal disorders.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Benjamin M. Stinson, Joseph J. Loparo
Summary: DNA double-strand breaks are mainly repaired through nonhomologous end joining (NHEJ) in vertebrates, which requires efficient end synapsis and processing mechanisms to maintain genome stability.
ANNUAL REVIEW OF BIOCHEMISTRY, VOL 90, 2021
(2021)
Review
Genetics & Heredity
Leonhard Andreas Karl, Martina Peritore, Lorenzo Galanti, Boris Pfander
Summary: DNA double strand breaks (DSBs) are repaired in eukaryotes by various cellular mechanisms. Nucleosome remodelers, which have the ability to slide, evict, position, or edit nucleosomes, have emerged as key regulators of DSB repair. The activities of nucleosome remodelers at DSBs have been found to impact the decision-making process of DSB repair.
FRONTIERS IN GENETICS
(2022)
Article
Genetics & Heredity
Michelle L. Swift, Kate Beishline, Jane Azizkhan-Clifford
Summary: This study demonstrates the importance of Sp1 phosphorylation by ATM in facilitating the interaction with p300 for DSB repair. The recruitment of p300 to DSBs by Sp1 is essential for modifying histones and recruiting repair factors. Depletion of Sp1 leads to defects in histone acetylation and recruitment of repair proteins, highlighting the critical role of Sp1 in regulating chromatin remodelers for proper DSB repair.
Article
Cell Biology
Melanie Rall-Scharpf, Thomas W. P. Friedl, Shahar Biechonski, Michael Denkinger, Michael Milyavsky, Lisa Wiesmueller
Summary: The gender gap in DNA repair and its changes with aging have distinct effects on men and women.
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
Biochemistry & Molecular Biology
Ioannis Emmanouilidis, Natalia Fili, Alexander W. Cook, Yukti Hari-Gupta, Alia dos Santos, Lin Wang, Marisa L. Martin-Fernandez, Peter J. I. Ellis, Christopher P. Toseland
Summary: Mammalian cells are constantly exposed to various DNA damaging events, leading to the activation of DNA repair pathways. Cas9-based genomic intervention allows for induced DSBs at defined quantities and locations across the human genome, utilizing custom-designed promiscuous guide RNAs based on in silico predictions. This provides a generic, low-cost, and rapid methodology for inducing controlled DNA damage in cell culture models.
Article
Biochemistry & Molecular Biology
Shan Huang, Kaihang Wang, Stephen L. Mayo
Summary: A recent study shows that CbAgo, a prokaryotic argonaute, can induce DNA interference and generate double-stranded breaks in target DNAs. The study demonstrates that CbAgo can cleave genome target sites and induce chromosome recombination in Escherichia coli. The findings suggest that the guide-directed cleavage of pAgo on the host genome is mutagenic and can be utilized in genetic manipulation.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Oncology
Jiali Qin, Jie Fan, Gang Li, Shanting Liu, Zhensheng Liu, Yao Wu
Summary: The study found that radiation exposure may lead to mutations in DNA double-strand break repair genes, resulting in decreased DSB repair capacity and increased risk of PTMC.
CANCER CELL INTERNATIONAL
(2021)
Article
Hematology
Yingchi Zhang, Yufeng Gao, Hui Zhang, Jingliao Zhang, Fuhong He, Ales Hnizda, Maoxiang Qian, Xiaoming Liu, Yoshihiro Gocho, Ching-Hon Pui, Tao Cheng, Qianfei Wang, Jun J. Yang, Xiaofan Zhu, Xin Liu
Article
Oncology
Ales Hnizda, Milan Fabry, Takaya Moriyama, Petr Pachl, Michael Kugler, Vitezslav Brinsa, David B. Ascher, William L. Carroll, Petr Novak, Marketa Zaliova, Jan Trka, Pavlina Rezacova, Jun J. Yang, Vaclav Veverka
Article
Rheumatology
Marie Zikanova, Dawn Wahezi, Arielle Hay, Blanka Stiburkova, Charles Pitts, Dita Musalkova, Vaclava Skopova, Veronika Baresova, Olga Souckova, Katerina Hodanova, Martina Zivna, Viktor Stranecky, Hana Hartmannova, Ales Hnizda, Anthony J. Bleyer, Stanislav Kmoch
Article
Multidisciplinary Sciences
Meirong Bai, Roman Vozdek, Ales Hnizda, Chenxiao Jiang, Bingying Wang, Ladislav Kuchar, Tiejun Li, Yuefan Zhang, Chase Wood, Liang Feng, Yongjun Dang, Dengke K. Ma
NATURE COMMUNICATIONS
(2018)
Article
Urology & Nephrology
Benjamin Cochran, Tereza Kovacikova, Katerina Hodanova, Martina Zivna, Ales Hnizda, Angela G. Niehaus, Alex Bonnecaze, Gowrie Balasubraminiam, Irene Ceballos-Picot, Amret Hawfield, Kendrah Kiddy, Stanislav Kmoch, Anthony J. Bleyer
CLINICAL NEPHROLOGY
(2018)
Article
Biochemistry & Molecular Biology
Petr Man, Milan Fabry, Irena Sieglova, Daniel Kavan, Petr Novak, Ales Hnizda
BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS
(2019)
Article
Oncology
Takaya Moriyama, Shuguang Liu, Jing Li, Julia Meyer, Xujie Zhao, Wentao Yang, Youming Shao, Richard Heath, Alet Hnizda, William L. Carroll, Jun J. Yang
MOLECULAR CANCER THERAPEUTICS
(2019)
Article
Biochemistry & Molecular Biology
Anna Pelet, Vaclava Skopova, Ulrike Steuerwald, Veronika Baresov, Mohammed Zarhrate, Jean-Marc Plaza, Ales Hnizda, Matyas Krijt, Olga Souckova, Flemming Wibrand, Guorio Andorsdottir, Frooi Joensen, David Sedlak, Anthony Bleyer, Stanislav Kmoch, Stanislas Lyonnet, Marie Zikanov
HUMAN MOLECULAR GENETICS
(2019)
Article
Urology & Nephrology
Martina Zivna, Kendrah Kidd, Mohamad Zaidan, Petr Vyletal, Veronika Baresova, Katerina Hodanova, Jana Sovova, Hana Hartmannova, Miroslav Votruba, Helena Treslova, Ivana Jedlickova, Jakub Sikora, Helena Hulkova, Victoria Robins, Ales Hnizda, Jan Zivny, Gregory Papagregoriou, Laurent Mesnard, Bodo B. Beck, Andrea Wenzel, Kalman Tory, Karsten Haeeffner, Matthias T. F. Wolf, Michael E. Bleyer, John A. Sayer, Albert C. M. Ong, Lidia Balogh, Anna Jakubowska, Agnieszka Laszkiewicz, Rhian Clissold, Charles Shaw-Smith, Raj Munshi, Robert M. Haws, Claudia Izzi, Irene Capelli, Marisa Santostefano, Claudio Graziano, Francesco Scolari, Amy Sussman, Howard Trachtman, Stephane Decramer, Marie Matignon, Philippe Grimbert, Lawrence R. Shoemaker, Christoforos Stavrou, Mayssa Abdelwahed, Neila Belghith, Matthew Sinclair, Kathleen Claes, Tal Kopel, Sharon Moe, Constantinos Deltas, Bertrand Knebelmann, Luca Rampoldi, Stanislav Kmoch, Anthony J. Bleyer
KIDNEY INTERNATIONAL
(2020)
Article
Biochemistry & Molecular Biology
Amanda K. Chaplin, Steven W. Hardwick, Shikang Liang, Antonia Kefala Stavridi, Ales Hnizda, Lee R. Cooper, Taiana Maia De Oliveira, Dimitri Y. Chirgadze, Tom L. Blundell
Summary: The study reveals the mechanism of how DNA-PKcs and the Ku70/80 heterodimer interact with DNA to repair DNA double-strand breaks, providing new insights into NHEJ.
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Roopa Thapar, Jing L. Wang, Michal Hammel, Ruiqiong Ye, Ke Liang, Chengcao Sun, Ales Hnizda, Shikang Liang, Su S. Maw, Linda Lee, Heather Villarreal, Isaac Forrester, Shujuan Fang, Miaw-Sheue Tsai, Tom L. Blundell, Anthony J. Davis, Chunru Lin, Susan P. Lees-Miller, Terence R. Strick, John A. Tainer
NUCLEIC ACIDS RESEARCH
(2020)
Review
Biochemistry & Molecular Biology
Shikang Liang, Amanda K. Chaplin, Antonia Kefala Stavridi, Robert Appleby, Ales Hnizda, Tom L. Blundell
Summary: This paragraph discusses the three structural aspects of the repair pathway for Non-homologous end joining (NHEJ), emphasizing the orchestration of DNA repair to ensure robust and efficient NHEJ. It also highlights the focus on structural studies over the past two decades, utilizing both X-ray diffraction and cryo-EM techniques to investigate macromolecular assemblies.
PROGRESS IN BIOPHYSICS & MOLECULAR BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Ales Hnizda, Petr Tesina, Thanh-Binh Nguyen, Zdenek Kukacka, Lukas Kater, Amanda Chaplin, Roland Beckmann, David B. Ascher, Petr Novak, Tom L. Blundell
Summary: Nonhomologous end joining (NHEJ) is a DNA repair mechanism that maintains genomic integrity, with the Ku70/80 complex playing a critical role in recognizing DNA breaks. Research has shown that the SAP domain in the Ku70 C-terminal region changes its position depending on DNA binding, potentially serving as a flexible entry gate for broken DNA.
Meeting Abstract
Biochemistry & Molecular Biology
P. Melenovska, J. Sokolova, J. Krijt, R. Vozdek, A. Hnizda, J. Kraus, T. Majtan, V. Kozich
EUROPEAN JOURNAL OF HUMAN GENETICS
(2018)
