Article
Biochemistry & Molecular Biology
Raquel Gago-Fuentes, Valentyn Oksenych
Summary: NHEJ factors XLF, DNA-PKcs, and PAXX play crucial roles in maintaining neural stem and progenitor cell populations and neurodevelopment in mammals, particularly evident in double knockout models.
Article
Cell Biology
Huaping Xiao, Fanghua Li, Emil Mladenov, Aashish Soni, Veronika Mladenova, Bing Pan, Rositsa Dueva, Martin Stuschke, Beate Timmermann, George Iliakis
Summary: The load of DNA double-strand breaks induced by ionizing radiation plays a key role in determining the repair pathway choice in higher eukaryotes. The integration of DNA-PKcs into resection regulation suggests a mechanism adaptively facilitating resection. Mutations in DNA-PKcs result in hyper-resection, ruling out the competition between c-NHEJ and HR as the cause of increased resection.
Review
Biochemistry & Molecular Biology
Go Watanabe, Michael R. Lieber
Summary: Nonhomologous DNA end joining is the major pathway for repairing double-strand breaks in cells, and Artemis serves as the major nuclease in this process. The activity of Artemis is tightly regulated by the DNA-PKcs kinase, which interacts with Artemis and is activated by broken DNA ends. Studying the structure of the Artemis:DNA-PKcs complex and its relevance to biochemistry and the immune system provides important insights into the cellular DNA repair process.
JOURNAL OF MOLECULAR BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Tizia Matthaeus, Sandra Stoesser, Hatice Yasemin Seren, Vivien M. M. Haberland, Andrea Hartwig
Summary: In this study, the negative effect of arsenite on BRCA1-mediated DNA damage response mechanisms was investigated. Arsenite treatment impaired the function of BRCA1, leading to a shift from error-free homologous recombination (HR) to error-prone non-homologous end-joining (NHEJ), which may compromise genomic stability.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
Cinzia Caggiano, Francesca Cavallo, Teresa Giannattasio, Gioia Cappelletti, Pellegrino Rossi, Paola Grimaldi, Darren R. Feldman, Maria Jasin, Marco Barchi
Summary: Germ cell tumors exhibit high sensitivity to cisplatin-based chemotherapy, but some patients develop resistance to treatment. By studying cisplatin-resistant TGCT cell lines, it was found that these cells showed reduced NHEJ repair pathway, lower expression of 53BP1 and DNA-PKcs proteins, and enhanced homologous recombination repair pathway, leading to resistance to PARP inhibitor monotherapy and potential benefits from combination therapy with low-dose cisplatin and PARPi.
Article
Biochemistry & Molecular Biology
Wei-Min Chen, Jui-Chung Chiang, Zengfu Shang, Guillermo Palchik, Ciara Newman, Yuanyuan Zhang, Anthony J. Davis, Hsinyu Lee, Benjamin P. C. Chen
Summary: DNA-PKcs plays a key role in DNA double-strand break repair and is involved in the cellular response to oxidative stress. It interacts with mitochondria proteins ANT2 and VDAC2 to maintain oxidative phosphorylation and mitochondrial membrane potential. The formation of the DAV complex is important for energizing the cell and its dissociation under oxidative stress helps reduce ROS production and promote cellular recovery.
Article
Oncology
Xiaoqing Li, Shitao Zou, Liangsu Zhou, Aidi Gao, Jing Xu, Chao He, Jundong Zhou, Shuhua Wu, Yihong Chen
Summary: This study found that high RAD18 expression is associated with a poorer prognosis in ESCC patients who received radiotherapy. Lowering RAD18 expression increased the sensitivity of ESCC cells to radiation and prolonged DNA damage repair time. RAD18 regulates radioresistance through non-homologous end joining pathway.
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)
Article
Biochemistry & Molecular Biology
Xiongxiong Liu, Chao Sun, Qiqi Wang, Ping Li, Ting Zhao, Qiang Li
Summary: This study aimed to investigate the role of Sp1 in the radioresistance of GBM cells. The results showed that Sp1 was upregulated after IR in vitro and in vivo, and knocking down Sp1 sensitized GBM cells to IR. Sp1 activated the DNA-PKcs promoter and increased its expression and activity. Additionally, the loss of Sp1 delayed DSB repair and increased IR-induced apoptosis of GBM cells. Overall, these findings suggest that Sp1 plays a crucial role in GBM radioresistance.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
Kyung Hwan Kim, Han Sang Kim, Seung-Seob Kim, Hyo Sup Shim, Andrew Jihoon Yang, Jason Joon Bock Lee, Hong In Yoon, Joong Bae Ahn, Jee Suk Chang
Summary: This study investigated the role of mutations in DNA damage repair genes on treatment outcomes after radiotherapy (RT). The results suggest that tumors with mutations in ATM and BRCA1/2 genes exhibit superior tumor response and local control after RT.
CANCER RESEARCH AND TREATMENT
(2022)
Review
Cell Biology
Wojciech M. Ciszewski, Katarzyna Sobierajska, Anna Stasiak, Waldemar Wagner
Summary: The presence of high levels of L-lactate in the cancer microenvironment has a characteristic feature, which can affect cancer cells through its receptoric and epigenetic modes of action and may be associated with drug resistance. Increased DNA repair capacity and enhanced drug efflux are important mechanisms for ineffective radiotherapy and drug-based therapies.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Aashish Soni, Xiaolu Duan, Martin Stuschke, George Iliakis
Summary: The activation of the intra-S-phase checkpoint is essential for maintaining genomic stability and involves the activities of ATM and ATR. DNA-PKcs also contributes to the recovery from the checkpoint. The organization of the intra-S-phase checkpoint is similar to that of the G(2) checkpoint.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Daniel Heylmann, Viviane Ponath, Thomas Kindler, Bernd Kaina
Summary: The research investigated the radiation sensitivity of different human blood cell populations obtained from healthy volunteers. T and B cells were found to be highly sensitive to radiation, but displayed DNA repair competence. In terms of cell death/apoptosis, T cells, NK cells, and B cells showed higher sensitivity compared to monocytes, macrophages, and immature dendritic cells.
SCIENTIFIC REPORTS
(2021)
Article
Ophthalmology
Ismahane Moulay Lakhdar, Melanie L. Ferlazzo, Joelle Al Choboq, Elise Berthel, Laurene Sonzogni, Clement Devic, Adeline Granzotto, Juliette Thariat, Nicolas Foray
Summary: This study aimed to investigate the radiosensitivity and the functionality of the ATM-dependent signaling and repair pathway of radiation-induced DNA double-strand breaks in skin fibroblasts derived from retinoblastoma (Rb) patients. Results showed significant cellular radiosensitivity, incomplete DSB recognition, delay in the ATM nucleo-shuttling, and exacerbated MRE11 nuclease activity in skin fibroblasts from Rb patients. Treatment with statin and bisphosphonates led to significant complementation of these impairments, suggesting the involvement of the ATM kinase in the radiosensitivity/radiosusceptibility phenotype observed in Rb cases.
CURRENT EYE RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Waldemar Wagner, Katarzyna Sobierajska, Katarzyna Dominika Kania, Edyta Paradowska, Wojciech Michal Ciszewski
Summary: The study reveals that lactate can decrease lentiviral transduction efficiency by increasing the nuclear localization of DNA-PKcs, and the stimulation of cells with HCA1 agonist or HDAC inhibitor can mimic this effect. Additionally, inhibiting lactate flux can also reduce the nuclear localization of DNA-PKcs, leading to diminished lentiviral transduction efficacy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)