Article
Cell Biology
Marta Llorens-Agost, Michael Ensminger, Hang Phuong Le, Anugrah Gawai, Jie Liu, Andres Cruz-Garcia, Sarita Bhetawal, Richard D. Wood, Wolf-Dietrich Heyer, Markus Loebrich
Summary: BRCA2-deficient cells are vulnerable to inactivation of DNA repair pathways for DSBs, which can be exploited clinically. RAD52 and BRCA2 regulate the TMEJ process by blocking the POL theta function, ensuring proper repair of DSBs in mitosis.
NATURE CELL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Huiming Lu, Qin Zhang, Daniel J. Laverty, Andrew C. Puncheon, Mathew M. Augustine, Gareth J. Williams, Zachary D. Nagel, Benjamin P. C. Chen, Anthony J. Davis
Summary: In this study, it was found that ATM drives the DNA damage response by modulating multiple signal transduction and DNA repair pathways. ATM phosphorylates DNA-PKcs at threonine 4102 (T4102) in response to DSBs, promoting NHEJ-dependent repair and increasing genomic stability. These findings highlight the key role of ATM in DNA repair.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Suleman S. Hussain, Rahul Majumdar, Grace M. Moore, Himanshi Narang, Erika S. Buechelmaier, Maximilian J. Bazil, Pavithran T. Ravindran, Jonathan E. Leeman, Yi Li, Manisha Jalan, Kyrie S. Anderson, Andrea Farina, Rekha Soni, Neeman Mohibullah, Edin Hamzic, Xiaoqing Rong-Mullins, Christopher Sifuentes, Rama R. Damerla, Agnes Viale, Simon N. Powell, Daniel S. Higginson
Summary: This study developed a Cas9-based repair system with simplified repair outcomes and converted it into ddPCR readouts for easier use in more laboratories. The experiment found that the key Alt-EJ factor Pol theta only accounts for 50% of total Alt-EJ, SSTR requires BRCA1 and MRE11 activity, and BRCA1 promotes Alt-EJ usage at two-ended DSBs.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Plant Sciences
Hira Khan, Takashi Ochi
Summary: Non-homologous end joining (NHEJ) is important for repairing DNA double-strand breaks in plants, but the molecular mechanism of plant NHEJ is still unclear. This study discovered a previously unidentified plant ortholog of PAXX, which has a similar structure to human PAXX but functions similar to human XLF by interacting with Ku70/80 and XRCC4. This suggests that plant PAXX combines the roles of mammalian PAXX and XLF, indicating a functional redundancy between PAXX and XLF in plants.
Article
Cell Biology
Kyung Yong Lee, Anindya Dutta
Summary: The cell-cycle phase plays a crucial role in determining repair pathway choice at DNA double-strand breaks, with Chk1 promoting non-homologous end joining (NHEJ) repair in the G1 phase. ASF1A, a histone chaperone, also promotes NHEJ independently of its chaperone activity. Chk1 phosphorylates ASF1A at Ser-166 in G1, enhancing its interaction with the repair protein MDC1 and promoting NHEJ repair.
Article
Microbiology
Changkun Hu, Taylor Bugbee, Dalton Dacus, Rachel Palinski, Nicholas Wallace
Summary: Beta human papillomavirus type 8 protein E6 (8E6) attenuates both homologous recombination (HR) and non-homologous end joining (NHEJ) DNA repair pathways, resulting in abnormal repair and increased deletions at DNA double strand breaks (DSBs). This study provides experimental evidence of this attenuation and demonstrates that 8E6 acts via p300 destabilization.
Article
Genetics & Heredity
Joseph J. Loparo
Summary: DNA double strand breaks (DSBs) are common lesions that can lead to cancer. The non-homologous end joining (NHEJ) pathway repairs the majority of these breaks by directly ligating DNA ends together. Recent advancements in single-molecule approaches and cryo-EM have improved our understanding of how DNA end synapsis and processing are coordinated in NHEJ, which is crucial for accurate repair.
Article
Cell Biology
You-hong Wang, Zhen Guo, Liang An, Yong Zhou, Heng Xu, Jing Xiong, Zhao-qian Liu, Xiao-ping Chen, Hong-hao Zhou, Xiong Li, Tao Liu, Wei-hua Huang, Wei Zhang
Summary: This study found that LINC-PINT is significantly downregulated in nasopharyngeal cancer tissues compared to rhinitis tissues, and low LINC-PINT expressions are associated with poorer prognosis in patients receiving radiotherapy. LINC-PINT plays a functional role in inhibiting malignant phenotypes and sensitizing cancer cells to irradiation in vitro and in vivo. Mechanistically, LINC-PINT inhibits DNA damage repair through the ATM/ATR-Chk1/Chk2 signaling pathways and increases radiosensitivity by interacting with DNA-PKcs.
CELL DEATH & DISEASE
(2021)
Review
Cell Biology
Stephanie M. Ackerson, Carlan Romney, P. Logan Schuck, Jason A. Stewart
Summary: Regulation of DNA double-strand breaks and telomeres in cells is diametrically opposed, with DSBs requiring quick recognition and repair while telomeres must be protected to prevent unwanted chromosome fusions. Decision on whether to join DNA ends is critical for genome stability, and processing of telomeres and DSBs share commonalities. Repair of DSBs is determined by decision points that shift towards homologous recombination (HR) or non-homologous end joining (NHEJ).
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Jenny Kaur Singh, Rebecca Smith, Magdalena B. Rother, Anton J. L. de Groot, Wouter W. Wiegant, Kees Vreeken, Ostiane D'Augustin, Robbert Q. Kim, Haibin Qian, Przemek M. Krawczyk, Roman Gonzalez-Prieto, Alfred C. O. Vertegaal, Meindert Lamers, Sebastien Huet, Haico van Attikum
Summary: The study reveals that PARP1-driven chromatin expansion facilitates the recruitment of ZNF384, which subsequently recruits Ku70/Ku80 to promote cNHEJ. This plays a crucial role in repairing DSBs and maintaining genome stability.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Chuxuan Li, Hanwen Zhu, Shikai Jin, Leora M. Maksoud, Nikhil Jain, Ji Sun, Yang Gao
Summary: DNA polymerase theta (Pol theta) plays a crucial role in the microhomology-mediated end joining (MMEJ) pathway for repairing DNA double-strand breaks. This study presents cryo-electron microscope structures of Lates calcarifer Pol theta, revealing its interactions with long and short DNA substrates and its similarity to high-fidelity A-family polymerases. Computational simulations and mutagenesis studies suggest that unique insertion loops of Pol theta stabilize short DNA binding and assemble the active site for MMEJ repair. These findings provide a structural basis for understanding Pol theta-mediated MMEJ.
NUCLEIC ACIDS RESEARCH
(2023)
Review
Oncology
Mohsen Valikhani, Elahe Rahimian, Seyed Esmaeil Ahmadi, Rouzbeh Chegeni, Majid Safa
Summary: Chromosomal translocations are the main cause of hematologic malignancies, resulting from aberrant DNA double-strand break repair. Defective NHEJ, HR, or A-EJ pathways may drive hematopoietic cells towards tumorigenesis. Targeting these repair pathways can potentially sensitize cancer cells, especially resistant clones, to radiation or chemotherapy agents.
EXPERIMENTAL HEMATOLOGY & ONCOLOGY
(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)
Article
Genetics & Heredity
Metztli Cisneros-Aguirre, Xiaoli Ping, Jeremy M. Stark
Summary: This review describes key factors that influence the steps of DSB EJ in mammalian cells, which is significant for understanding mutagenesis resulting from clastogenic cancer therapeutics and for developing gene editing approaches.
Article
Plant Sciences
Fabienne Gehrke, Angelina Schindele, Holger Puchta
Summary: Heritable plant chromosome engineering can be achieved in somatic cells using CRISPR/Cas to induce nonhomologous double-strand break repair pathways. This technology allows for large-scale restructuring of plant chromosomes, including duplications, inversions, and translocations. The use of nonhomologous end joining pathways in somatic cells facilitates efficient chromosomal rearrangements. This breakthrough has the potential to revolutionize plant breeding.
Article
Biology
Hisayo Tsuchiya, Mikio Shimada, Kaima Tsukada, Qingmei Meng, Junya Kobayashi, Yoshihisa Matsumoto
Summary: The dose-rate effect refers to the reduction of biological effects of ionizing radiation, such as X-ray and gamma-ray, as the dose rate is decreased. The mechanisms underlying this effect, particularly in terms of DNA damage repair, remain to be fully understood. Ku proteins are thought to play a role in the dose-rate effect, as observed in rodent cells deficient in Ku70, Ku86, and DNA-PKcs.
JOURNAL OF RADIATION RESEARCH
(2021)
Article
Biotechnology & Applied Microbiology
Kaima Tsukada, Mikio Shimada, Rikiya Imamura, Kotaro Saikawa, Masamichi Ishiai, Yoshihisa Matsumoto
Summary: PNKP is recruited to DNA damage sites via interactions between its FHA domain and XRCC1 or XRCC4, playing a crucial role in DNA repair and maintenance of genome stability.
MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS
(2021)
Editorial Material
Oncology
Yoshihisa Matsumoto, Atsushi Shiozaki, Eigo Otsuji
ANNALS OF SURGICAL ONCOLOGY
(2021)
Article
Oncology
Yoshihisa Matsumoto, Atsushi Shiozaki, Toshiyuki Kosuga, Michihiro Kudou, Hiroki Shimizu, Tomohiro Arita, Hirotaka Konishi, Shuhei Komatsu, Takeshi Kubota, Hitoshi Fujiwara, Kazuma Okamoto, Mitsuo Kishimoto, Eiichi Konishi, Eigo Otsuji
Summary: Overexpression of CFTR in ESCC activates the p38 signaling pathway and is associated with a good patient prognosis. CFTR shows potential as a mediator and/or a biomarker for ESCC. Immunohistochemical analysis revealed a relationship between the CFTR expression pattern and pN category, as well as a correlation between weak CFTR expression at the invasive front and shorter postoperative survival.
ANNALS OF SURGICAL ONCOLOGY
(2021)
Article
Cell & Tissue Engineering
Tomoko Miyake, Munekazu Kuge, Yoshihisa Matsumoto, Mikio Shimada
Summary: Research indicates that AGR can increase the viability of induced pluripotent stem cells (iPSCs) and induce the expression of genes related to differentiation.
STEM CELL RESEARCH
(2021)
Review
Biochemistry & Molecular Biology
Yoshihisa Matsumoto
Summary: DNA double-strand break (DSB) is a serious type of DNA damage caused by ionizing radiation and certain anticancer drugs. DNA-PK plays a crucial role in DSB repair and can be inhibited to increase cellular sensitivity to radiotherapy and chemotherapy. Small molecule inhibitors targeting DNA-PK have been developed and some are currently in clinical trials.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Clinical Neurology
Yusuke Otsu, Yoshihisa Matsumoto, Koichi Higaki, Takuya Furuta, Mayuko Moritsubo, Hidenobu Yoshitake, Yui Nagata, Takuro Hashikawa, Hideki Sakai, Setsuko Nakagawa, Kenji Takahashi, Yasuo Sugita
Summary: This study reports two cases of gliosarcoma, a type of tumor with alternating glial and mesenchymal components. The pathological analysis revealed different types of glial components in each case, highlighting the importance of continued histopathological and genetic evaluation of gliosarcoma.
Article
Radiology, Nuclear Medicine & Medical Imaging
Shogo Tsunemine, Shuichi Ozawa, Minoru Nakao, Hideharu Miura, Akito Saito, Daisuke Kawahara, Yasuhiko Onishi, Takashi Onishi, Taiki Hashiguchi, Yoshihisa Matsumoto, Tsutomu Maruta, Yuji Murakami, Yasushi Nagata
Summary: This study evaluates the effect of different air computed tomography (CT) numbers on the dose calculation of head-and-neck radiotherapy. The results indicate that IVDToutair (MVCT) is more accurate than IVDTinair (MVCT) in recalculating the dose.
JOURNAL OF APPLIED CLINICAL MEDICAL PHYSICS
(2023)
Article
Environmental Sciences
Hisayo Tsuchiya, Mikio Shimada, Kaima Tsukada, Qingmei Meng, Junya Kobayashi, Yoshihisa Matsumoto
Summary: It is commonly accepted that the biological effects of ionizing radiation decrease as the dose rate becomes lower. Recent research suggests that the repair of DNA damage through non-homologous end joining (NHEJ) may play a role in this dose-rate effect.
RADIATION PROTECTION DOSIMETRY
(2022)
Article
Oncology
Sadamoto Zenda, Yasunori Arai, Shunsuke Sugawara, Yoshitaka Inaba, Kazuki Hashimoto, Kouji Yamamoto, Yusuke Saigusa, Takashi Kawaguchi, Sanae Shimada, Marie Yokoyama, Tempei Miyaji, Tomoka Okano, Naoki Nakamura, Eisuke Kobayashi, Tatsuya Takagi, Yoshihisa Matsumoto, Yosuke Uchitomi, Miyuki Sone
Summary: This article describes a study protocol to investigate the efficacy and safety of transcatheter arterial embolization (TAE) for pain relief in patients with bone metastases. The study will enroll eligible patients and assess pain relief and the occurrence of adverse events after TAE treatment.
Article
Biology
Mikio Shimada, Takumi Tokumiya, Tomoko Miyake, Kaima Tsukada, Norie Kanzaki, Hiromi Yanagihara, Junya Kobayashi, Yoshihisa Matsumoto
Summary: In this study, the researchers found that depleting the RAD18 gene in iPSCs and NPCs resulted in a decreased mutation frequency, revealing the function of RAD18 in pluripotent stem cells.
JOURNAL OF RADIATION RESEARCH
(2023)
Article
Biology
Kai Nishikubo, Maho Hasegawa, Yudai Izumi, Kentaro Fujii, Koichi Matsuo, Yoshihisa Matsumoto, Akinari Yokoya
Summary: This study investigated the structural features of wild-type and phospho-mimicking mutated XRCC4 protein, which is involved in DNA double-strand break repair. XRCC4 with a HisTag was expressed and purified using E. coli. Phospho-mimicking mutants were also prepared to reproduce the negative charge resulting from phosphorylation. The results suggest that beta-strand structure stabilizes the multimerization of XRCC4 and is regulated by phosphorylation at the C-terminal site.
INTERNATIONAL JOURNAL OF RADIATION BIOLOGY
(2023)
Article
Biology
Rikiya Imamura, Mizuki Saito, Mikio Shimada, Junya Kobayashi, Masamichi Ishiai, Yoshihisa Matsumoto
Summary: APTX, the product of the causative gene for hereditary neurogenerative syndromes, is involved in DNA repair and has enzymatic activity. It physically binds to XRCC1 and XRCC4, suggesting its role in DNA strand break repair. The significance of APTX in double-strand break repair (DSBR) and its interaction with XRCC4 have not been fully understood.
JOURNAL OF RADIATION RESEARCH
(2023)
Article
Environmental Sciences
Megha Mathur, Neha Rawat, Tanushree Saxena, Renu Khandelwal, Neha Jain, Mukesh K. Sharma, Medicherla K. Mohan, Pradeep Bhatnagar, Swaran J. S. Flora, Pallavi Kaushik
Summary: Fluoride and arsenic are two major contaminants of water and soil systems, causing potential toxicity to organisms. Microorganisms that can tolerate toxic stress and mineralize contaminants can restore contaminated soil systems. It was found that arsenic has an antagonistic effect on the toxicity of fluoride.
Meeting Abstract
Environmental Sciences
Takayoshi Suzuki, Yoshihisa Matsumoto
ENVIRONMENTAL AND MOLECULAR MUTAGENESIS
(2022)