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
Multidisciplinary Sciences
Ming Tang, Guofang Chen, Bo Tu, Zhiyi Hu, Yujia Huang, Christopher C. DuFort, Xiaoping Wan, Zhiyong Mao, Yongzhong Liu, Wei-Guo Zhu, Wen Lu
Summary: DDR has different effects on cancer susceptibility and drug resistance. Recent studies showed that DDR inhibitors impact immune surveillance, however, the underlying mechanism is poorly understood. This study reveals that methyltransferase SMYD2 plays a crucial role in nonhomologous end joining repair (NHEJ), promoting tumor cell adaptability to radiotherapy. SMYD2 is mobilized to chromatin upon DNA damage and methylates Ku70, leading to increased recruitment of Ku70/Ku80/DNA-PKcs complex. Inhibition of SMYD2 or knockdown of SMYD2 results in persistent DNA damage and improper repair, leading to cytosolic DNA accumulation and activation of cGAS-STING pathway, triggering antitumor immunity by infiltration and activation of cytotoxic CD8+ T cells. This study reveals a novel role of SMYD2 in regulating NHEJ pathway and innate immune responses, suggesting SMYD2 as a promising therapeutic target for cancer treatment.
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
Dipayan Ghosh, Sathees C. Raghavan
Summary: This article discusses key proteins in the NHEJ repair pathway, such as PAXX, MRI/CYREN, TDP-43, IFFO1, ERCC6L2, and RNase H2, and their roles in the repair of double-strand breaks in the cell nucleus.
TRENDS IN GENETICS
(2021)
Article
Genetics & Heredity
Christina A. Gerodimos, Go Watanabe, Michael R. Lieber
Summary: The nucleosomal state imposes strict constraints on NHEJ nuclease and ligase activities, and the presence of nucleosome-wrapped DNA ends can affect the joining process.
Article
Biochemistry & Molecular Biology
Maria Ovejero-Sanchez, Jorge Rubio-Heras, Maria del Carmen Vicente de la Pena, Laura San-Segundo, Jesus Perez-Losada, Rogelio Gonzalez-Sarmiento, Ana Belen Herrero
Summary: Ovarian cancer is a deadly malignancy that requires more effective treatments. The combination of chloroquine with nonhomologous end joining inhibitors has been found to inhibit proliferation and induce apoptosis in ovarian cancer cell lines. Additionally, the combination with a pan-histone deacetylase inhibitor enhances the efficacy of chloroquine. These drug combinations could represent new therapeutic strategies against ovarian cancer.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell & Tissue Engineering
Sebastiano Giallongo, Daniela Rehakova, Tommaso Biagini, Oriana Lo Re, Priyanka Raina, Gabriela Lochmanova, Zbynek Zdrahal, Igor Resnick, Pille Pata, Illar Pata, Martin Mistrik, Joao Pedro de Magalhaes, Tommaso Mazza, Irena Koutna, Manlio Vinciguerra
Summary: The study identifies the splicing isoform macroH2A1.1 as a potential regulator of DNA damage repair (DDR) during iPSC reprogramming. MacroH2A1.1 overexpression enhances DDR efficiency through specific activation of the nonhomologous end joining (NHEJ) repair pathway. It also improves iPSC reprogramming, indicating its importance in maintaining genome stability and therapeutic potential.
Article
Microbiology
Wen-Wei Zhang, Douglas G. Wright, Lynn Harrison, Greg Matlashewski
Summary: In this study, it was found that the protozoan parasite Leishmania lacks a functional NHEJ pathway but retains Ku70 and Ku80 proteins. Ku is involved in DSB repair and affects the repair outcome through different mechanisms. Additionally, Ku is required for the healthy growth of the parasite but is not important for maintaining telomere lengths.
Article
Biochemical Research Methods
Xiaoqin Liu, Mengmeng Liu, Jin Zhang, Yizhao Chang, Zhiyong Cui, Boyang Ji, Jens Nielsen, Qingsheng Qi, Jin Hou
Summary: The study revealed the distribution of NHEJ-mediated integration on chromosomes for the first time and demonstrated its potential for constructing a genome-scale trackable mutagenesis library. The research showed that the integration inserts DNA randomly across chromosomes and exhibits a preference for transcriptional regulatory regions. This approach proved to be effective in rapidly identifying new targets for improving beta-carotene biosynthesis and acetic acid tolerance.
ACS SYNTHETIC BIOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Daniel Abegg, Martin Tomanik, Nan Qiu, Dany Pechalrieu, Anton Shuster, Bruno Commare, Antonio Togni, Seth B. Herzon, Alexander Adibekian
Summary: The tetrafluoroalkyl benziodoxole (TFBX) has emerged as a powerful cysteine-selective chemoproteomic probe, featuring superior target occupancy, faster labeling kinetics, and broader proteomic coverage compared to traditional cysteine-reactive probes. This new probe has been demonstrated to successfully identify cellular targets of (-)-myrocin G, leading to the discovery of the first reported inhibitors of the biomedically important protein XRCC5. Additionally, this probe disrupts the interaction of XRCC5 with DNA, sensitizing cancer cells to chemotherapeutic agents and UV-light-induced DNA damage.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Genetics & Heredity
Danyu Song, Xiaomei Li, Wei Wei, Xueqin Liu, Lin Wu, Hui Xiong
Summary: In this study, two siblings with Emery-Dreifuss muscular dystrophy (EDMD) were reported in a family, with one showing symptoms of heart dilation and muscle weakness, while the other had elevated levels of creatine kinase. Genetic analysis revealed complete deletion of the EMD gene and a rearrangement in the FLNA gene in both patients, supporting the pathogenic mechanism of microhomology-mediated nonhomologous end joining.
FRONTIERS IN GENETICS
(2021)
Article
Cell Biology
Muddenahalli Srinivasa Sudhanva, Gurusamy Hariharasudhan, Semo Jun, Gwanwoo Seo, Radhakrishnan Kamalakannan, Hyun Hee Kim, Jung-Hee Lee
Summary: This study demonstrates that miR-145 suppresses DNA-PKcs expression, affecting DNA double-strand break repair and rendering cells sensitive to ionizing radiation. Additionally, miR-145 inhibition is associated with increased Akt1 phosphorylation and upregulation of DNA-PKcs in cancer cells.
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
Andrology
Hui-Yu Dong, Pan Zang, Mei-Ling Bao, Tian-Ren Zhou, Chen-Bo Ni, Lei Ding, Xu-Song Zhao, Jie Li, Chao Liang
Summary: Recent studies have found that the combination of anti-androgen enzalutamide and PARP inhibitor olaparib can significantly inhibit the proliferation and induce apoptosis in AR-positive prostate cancer cells. Bioinformatics analysis revealed that the combination treatment affects nonhomologous end joining and apoptosis pathways. Moreover, enzalutamide enhances the response of prostate cancer cells to the combination therapy by regulating anti-apoptotic and pro-apoptotic genes.
ASIAN JOURNAL OF ANDROLOGY
(2023)
Article
Biochemistry & Molecular Biology
Yalin Zhu, Hongdan Dai, Yonghong Wang, Yang Liang, Wenli Feng, Ying Yuan
Summary: The study discovered abnormal upregulation of FEN1 in CML, its involvement in the Alt-EJ repair pathway, and the knockdown of FEN1 not only inhibited proliferation and induced apoptosis but also enhanced drug efficacy in resistant cells. There was also excessive DSB accumulation after FEN1 inhibition, indicating its promising therapeutic potential in CML treatment and extending understanding of abnormal DSB repair for cancer treatment.
DNA AND CELL BIOLOGY
(2021)