Article
Multidisciplinary Sciences
Aviv Meir, J. Brooks Crickard, Youngho Kwon, Patrick Sung, Eric C. Greene
Summary: Srs2 is a crucial DNA repair enzyme that regulates the formation of homologous recombination intermediates by removing a recombinase called Rad51. Recent research indicates that two motor proteins, Rad54 and Rdh54, can restrict the activity of Srs2 and facilitate the progression of recombination.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biochemistry & Molecular Biology
Gabriel Matos-Rodrigues, Vilma Barroca, Ali-Akbar Muhammad, Elodie Dardillac, Awatef Allouch, Stephane Koundrioukoff, Daniel Lewandowski, Emmanuelle Despras, Josee Guirouilh-Barbat, Lucien Frappart, Patricia Kannouche, Pauline Dupaigne, Eric Le Cam, Jean-Luc Perfettini, Paul-Henri Romeo, Michelle Debatisse, Maria Jasin, Gabriel Livera, Emmanuelle Martini, Bernard S. Lopez
Summary: In this study, a mouse model with an inducible dominant-negative form of RAD51 was engineered to suppress RAD51-mediated homologous recombination. The results showed that RAD51 activity is important for maintaining progenitor cell homeostasis, preventing aging, and balancing cancer and aging.
Article
Cell Biology
Wei-Ting Chen, Huan-Yi Tseng, Chung-Lin Jiang, Chih-Ying Lee, Peter Chi, Liuh-Yow Chen, Kai-Yin Lo, I-Ching Wang, Fu-Jung Lin
Summary: Elp1 depletion exacerbates genomic instability, resulting in chromosome breakage and genotoxic stress-induced DNA fragmentation upon exposure to ionizing radiation (IR). Elp1-deficient cells are sensitive to DNA damage, exhibit impaired cell proliferation, and have defective HR repair. Elp1 regulates RAD51 expression by promoting its translation in response to DNA damage.
JOURNAL OF BIOMEDICAL SCIENCE
(2021)
Article
Multidisciplinary Sciences
Wan-Chen Li, Chia-Yi Lee, Wei-Hsuan Lan, Tai-Ting Woo, Hou-Cheng Liu, Hsin-Yi Yeh, Hao-Yen Chang, Yu-Chien Chuang, Chiung-Ya Chen, Chi-Ning Chuang, Chia-Ling Chen, Yi-Ping Hsueh, Hung-Wen Li, Peter Chi, Ting-Fang Wang
Summary: Most eukaryotes possess two RecA-like recombinases for interhomolog recombination during meiosis, but some have lost Dmc1. TrRad51 in Trichoderma reesei plays a crucial role in interhomolog recombination and has better mismatch tolerance than ScRad51, evolving ScDmc1-like properties through structural variations.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Review
Genetics & Heredity
Upasana Roy, Eric C. Greene
Summary: Homologous recombination (HR) is a crucial mechanism for the accurate repair of DNA double-stranded breaks and maintenance of genome integrity, with Rad51 recombinase playing a key role in eukaryotes. Rad51 paralogs, such as Rad55-Rad57 complex in yeast, regulate proper levels of HR and mutations in these genes are associated with diseases. Studies on Rad55-Rad57 in yeast have provided important insights into the conserved role of Rad51 paralogs in higher eukaryotes.
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
Biochemistry & Molecular Biology
Munan Shi, Jiajia Hou, Weichu Liang, Qianwen Li, Shan Shao, Shusheng Ci, Chuanjun Shu, Xingqi Zhao, Shanmeizi Zhao, Miaoling Huang, Congye Wu, Zhigang Hu, Lingfeng He, Zhigang Guo, Feiyan Pan
Summary: Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is identified as a regulator of HR repair through HDAC1-dependent regulation of RAD51 stability. SRC signaling activates GAPDH nuclear translocation, which binds with HDAC1 to prevent RAD51 degradation. These findings reveal the importance of GAPDH in HR repair.
Review
Biotechnology & Applied Microbiology
Erica S. Tsang, Pamela N. Munster
Summary: RAD51 plays a crucial role in homologous recombination DNA damage repair and is of great interest in oncology as a biomarker and potential therapeutic target. This review focuses on the development of RAD51 inhibitors, including novel molecules and ongoing clinical trials. Although identifying effective direct RAD51 inhibitors remains challenging, there may be a role for pharmacological indirect RAD51 inhibition in clinical practice.
ONCOTARGETS AND THERAPY
(2022)
Article
Biochemistry & Molecular Biology
Mingang Pan, Yu Sha, Jianguo Qiu, Yunmeng Chen, Lele Liu, Muyu Luo, Ailong Huang, Jie Xia
Summary: In this study, it was found that RAD51 is upregulated in HCC and its silencing or inhibition can reduce HCC cell proliferation, migration, invasion, and promote cell apoptosis and DNA damage. Combining RAD51 inhibition with sorafenib demonstrates a synergistic effect in inhibiting HCC progression. Furthermore, RAD51 knockdown affects various cellular pathways involved in apoptosis, DNA damage, and cell cycle regulation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cell Biology
Ah Reum Lee, Ji-Hoon Park, Sung Han Shim, Kwonho Hong, Hyeonwoo La, Kyung-Soon Park, Dong Ryul Lee
Summary: The study found that the activity of Rad 51 is lower in SCNT eggs and a significantly lower level of DSBs in SCNT embryos during reprogramming. Supplementation with RS-1 during the activation of SCNT embryos can increase RAD51 expression and DSB foci, thereby improving the efficiency of SCNT reprogramming. Through single-cell RNA-seq analysis, reactivation of genes and involvement of histone demethylase in reducing reprogramming-resistant regions were observed, which may contribute to overcoming developmental block and enhancing cell sources for regenerative medicine.
CELL PROLIFERATION
(2021)
Article
Biochemistry & Molecular Biology
Min Kim, Seung-Cheol Jee, Min-Kyoung Shin, Dong-Hee Han, Kyung-Bin Bu, Seung-Cheol Lee, Bo-Young Jang, Jung-Suk Sung
Summary: In this study, it was found that quercetin and isorhamnetin can promote the repair of B[a]P-induced DNA DSBs by modulating the expression levels of genes involved in DNA repair, especially RAD51. They also exert a protective effect by downregulating miR-34a, which downregulates RAD51.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biology
Enjie Li, Mingyue Xia, Yu Du, Kaili Long, Feng Ji, Feiyan Pan, Lingfeng He, Zhigang Hu, Zhigang Guo
Summary: This study reveals the involvement of METTL3 in the regulation of homologous recombination repair (HR) and chemotherapeutic response in breast cancer cells. It also demonstrates the role of METTL3 in the m6A modification of the EGF/RAD51 axis, which affects HR activity and DNA damage.
Review
Biochemistry & Molecular Biology
Hideo Tsubouchi
Summary: Homologous recombination (HR) is crucial for meiosis and is induced during meiotic prophase. The Hop2-Mnd1 complex, originally identified in budding yeast, is conserved across species and plays an essential role in meiosis. Accumulating evidence suggests that Hop2-Mnd1 promotes RecA-like recombinases for homology search and strand exchange. This review summarizes studies on the mechanism of the Hop2-Mnd1 complex in promoting HR and beyond.
Article
Biochemistry & Molecular Biology
Chaoyou Xue, Lucia Molnarova, Justin B. Steinfeld, Weixing Zhao, Chujian Ma, Mario Spirek, Kyle Kaniecki, Youngho Kwon, Ondrej Belan, Katerina Krejci, Simon J. Boulton, Patrick Sung, Eric C. Greene, Lumir Krejci
Summary: RECQ5 is identified as an ATP-dependent single-stranded DNA motor protein that can translocate on various nucleoprotein complexes and dismantle RAD51-ssDNA filaments. Protein-protein interaction with RAD51 is crucial for RECQ5's functions, but its substrate specificity and ability to remove certain mutant RAD51 proteins suggest a complex regulatory role in genome maintenance.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Chin-Chuan Chen, Chi-Yuan Chen, Shu-Fang Cheng, Tzong-Ming Shieh, Yann-Lii Leu, Wen-Yu Chuang, Kuang-Ting Liu, Shir-Hwa Ueng, Yin-Hwa Shih, Li-Fang Chou, Tong-Hong Wang
Summary: The study identified a natural compound, HGK, that can inhibit DDR in liver cancer cells and enhance their sensitivity to doxorubicin without producing any physiological toxicity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Koichi Sato, Inger Brandsma, Sari E. Van Rossum-Fikkert, Nicole Verkaik, Anneke B. Oostra, Josephine C. Dorsman, Dik C. van Gent, Puck Knipscheer, Roland Kanaar, Alex Zelensky
NUCLEIC ACIDS RESEARCH
(2020)
Article
Genetics & Heredity
Alex N. Zelensky, Mascha Schoonakker, Inger Brandsma, Marcel Tijsterman, Dik C. van Gent, Jeroen Essers, Roland Kanaar
Article
Medicine, Research & Experimental
Paula K. Bautista-Nino, Eliana Portilla-Fernandez, Eloisa Rubio-Beltran, Janette J. van der Linden, Rene de Vries, Richard van Veghel, Martine de Boer, Matej Durik, Yanto Ridwan, Renata Brandt, Jeroen Essers, Robert Menzies, Rachel Thomas, Alain de Bruin, Dirk J. Duncker, Heleen M. M. van Beusekom, Mohsen Ghanbari, Jan H. J. Hoeijmakers, Radislav Sedlacek, Rhian M. Touyz, Augusto C. Montezano, Ingrid van der Pluijm, A. H. Jan Danser, Kristian A. Haanes, Anton J. M. Roks
Article
Multidisciplinary Sciences
Humberto Sanchez, Kaley McCluskey, Theo van Laar, Edo van Veen, Filip M. Asscher, Belen Solano, John F. X. Diffley, Nynke H. Dekker
Summary: The study demonstrates the dynamics of the origin recognition complex and subsequent intermediates leading to the loading of an MCM helicase onto DNA using single-molecule optical trapping and confocal microscopy. ORC is shown to be a mobile protein that diffuses rapidly along DNA, with recruitment of MCM molecules in a ORC- and Cdc6-dependent way resulting in slow-moving ORC-MCM intermediates and rapidly scanning MCMs on DNA.
NATURE COMMUNICATIONS
(2021)
Article
Multidisciplinary Sciences
Rania Ghouil, Simona Miron, Lieke Koornneef, Jasper Veerman, Maarten W. Paul, Marie-Helene Le Du, Esther Sleddens-Linkels, Sari E. Van Rossum-Fikkert, Yvette van Loon, Natalia Felipe-Medina, Alberto M. Pendas, Alex Maas, Jeroen Essers, Pierre Legrand, Willy M. Baarends, Roland Kanaar, Sophie Zinn-Justin, Alex N. Zelensky
Summary: BRCA2 and its interactor HSF2BP are essential for meiotic recombination, with a high-affinity oligomerization-inducing interaction between the two proteins, but a repeat region in BRCA2 is not essential for mouse meiosis.
NATURE COMMUNICATIONS
(2021)
Article
Biology
Maarten W. Paul, Arshdeep Sidhu, Yongxin Liang, Sarah E. Van Rossum-Fikkert, Hanny Odijk, Alex N. Zelensky, Roland Kanaar, Claire Wyman
Summary: BRCA2 plays a crucial role in genome maintenance, homologous recombination, and replication fork protection. The absence of C-terminal domain does not significantly affect BRCA2 mobility and DNA-damage-induced immobile fraction increase, but leads to reduced HR function in cells.
Review
Cell Biology
Aditya N. Mhaskar, Lieke Koornneef, Alex N. Zelensky, Adriaan B. Houtsmuller, Willy M. Baarends
Summary: Meiotic DNA double-strand breaks are induced in a programmed and specifically orchestrated manner, with subsequent homologous recombination repair involving the preferred use of the homolog over the sister chromatid. The initial steps in homology recognition during meiotic homologous recombination require cooperation between the strand exchange proteins RAD51 and DMC1.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Judith M. A. Verhagen, Joyce Burger, Jos A. Bekkers, Alexander T. den Dekker, Jan H. von der Thuesen, Marina Zajec, Hennie T. Brueggenwirth, Marianne L. T. van der Sterre, Myrthe van den Born, Theo M. Luider, Wilfred F. J. van IJcken, Marja W. Wessels, Jeroen Essers, Jolien W. Roos-Hesselink, Ingrid van der Pluijm, Ingrid M. B. H. van de Laar, Erwin Brosens
Summary: The aim of this study was to uncover the molecular mechanisms underlying aneurysm formation in Marfan syndrome (MFS). By analyzing gene and protein expression, as well as cellular respiration experiments, we found that inflammation and mitochondrial dysfunction play important roles in the pathophysiological processes of aortic disease.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Medicine, General & Internal
Vinamr Rastogi, Sanne J. M. Stefens, Judith Houwaart, Hence J. M. Verhagen, Jorg L. de Bruin, Ingrid van der Pluijm, Jeroen Essers
Summary: Aortic aneurysms are dilations of the aorta that can be fatal upon rupture. Diagnostic radiological techniques such as ultrasound, MRI, and CT are used for early diagnosis and follow-up, but have limitations in predicting aneurysm enlargement or rupture risk. Molecular imaging techniques show potential for understanding aneurysm pathogenesis and facilitating early diagnostic analysis.
FRONTIERS IN MEDICINE
(2022)
Article
Genetics & Heredity
Tim Heemskerk, Gerarda van de Kamp, Jeroen Essers, Roland Kanaar, Maarten W. Paul
Summary: Live-cell and high-resolution fluorescence microscopy are powerful tools for studying DNA double-strand break repair. This review focuses on mammalian cell studies and discusses methods for inducing DNA double-strand breaks, visualizing and quantifying repair processes, and recent developments in super-resolution imaging and single-molecule tracking.
Article
Multidisciplinary Sciences
Humberto Sanchez, Zhaowei Liu, Edo van Veen, Theo van Laar, John F. X. Diffley, Nynke H. Dekker
Summary: The study investigates the impact of chromatinizing origins of replication on ORC and MCM at the single-molecule level. The mobility of ORC is reduced, but its binding to the origin remains unchanged. MCM is efficiently recruited and spatially confined to the origin.
NATURE COMMUNICATIONS
(2023)
Proceedings Paper
Computer Science, Artificial Intelligence
Tijmen H. de Wolf, Matthijs Snelders, Jeroen Essers, Ihor Smal
Summary: Cardiovascular diseases are a leading cause of death, and there is a need for classification systems to distinguish healthy and diseased cardiomyocytes for drug development and screening. Machine learning has been explored for this application, but its predictions lack interpretability and insight into the differences between healthy and diseased cardiomyocytes. To address this, researchers propose Contraction Analysis LIME (CA-LIME) to make machine learning algorithms more interpretable. CA-LIME is specifically designed for contraction analysis data and has shown applicability in explaining the effects of drugs and patient-specific diseased conditions.
2023 IEEE 20TH INTERNATIONAL SYMPOSIUM ON BIOMEDICAL IMAGING, ISBI
(2023)
Review
Chemistry, Multidisciplinary
Adelaide Miranda, Ana I. Gomez-Varela, Andreas Stylianou, Liisa M. Hirvonen, Humberto Sanchez, Pieter A. A. De Beule
Summary: The invention of the Atomic Force Microscope (AFM) in 1986 allowed for the study of cellular specimens under nearly physiological conditions with nanometric resolution, and the application of AFM to biological research expanded with improvements in imaging modes. Advances in super-resolution fluorescence microscopy techniques have brought the resolution of light microscopy to a level comparable to that of AFM, leading to the combination of AFM with fluorescence based super-resolution microscopy modalities.
