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)
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.
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
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
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
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
Biochemistry & Molecular Biology
Melania Balzarolo, Sander Engels, Anja J. de Jong, Katka Franke, Timo K. van den Berg, Muhammet F. Gulen, Andrea Ablasser, Edith M. Janssen, Bas van Steensel, Monika C. Wolkers
Summary: The methylation of m6A in DNA enhances immunogenicity in murine immune cells, with the response being sequence-specific. This feature of epigenetic alterations in DNA could potentially be utilized for designing immune-modulating therapeutics.
Review
Oncology
Meghana Manjunath, Bibha Choudhary, Sathees C. Raghavan
Summary: SCR7 is a potent anticancer agent that effectively inhibits NHEJ repair pathway by targeting Ligase IV. It has shown to be effective in blocking DNA repair in vitro and ex vivo, as well as improving genome editing using CRISPR-Cas system. Its wide applications and unique properties make it a valuable tool in cancer research and genome editing.
Article
Chemistry, Multidisciplinary
Yusuke Takezawa, Lingyun Hu, Takahiro Nakama, Mitsuhiko Shionoya
Summary: This study successfully reshaped a compactly-folded 8-17 DNAzyme into a metal-responsive allosteric DNAzyme by introducing a CuII-meditated unnatural base pair. The activity of the modified DNAzyme was enhanced by the addition of CuII ions, demonstrating good metal responsiveness. This research has significant implications for the practical application of modifying compactly folded DNAzymes.
CHEMICAL COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Duncan E. Scott, Nicola J. Francis-Newton, May E. Marsh, Anthony G. Coyne, Gerhard Fischer, Tommaso Moschetti, Andrew R. Bayly, Timothy D. Sharpe, Kalina T. Haas, Lorraine Barber, Chiara R. Valenzano, Rajavel Srinivasan, David J. Huggins, Miyoung Lee, Amy Emery, Bryn Hardwick, Matthias Ehebauer, Claudio Dagostin, Alessandro Esposito, Luca Pellegrini, Trevor Perrior, Grahame McKenzie, Tom L. Blundell, Marko Hyvonen, John Skidmore, Ashok R. Venkitaraman, Chris Abell
Summary: The study identifies CAM833 as an orthosteric inhibitor of RAD51:BRC, which affects DNA repair and potentiates cell death induced by DNA damage, working in coordination with PARP1 inhibitors to suppress growth in BRCA2-wildtype cells.
CELL CHEMICAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Xiaoli Gan, Yueyue Zhang, Donghao Jiang, Jingyao Shi, Han Zhao, Chengyu Xie, Yanyan Wang, Jingyan Xu, Xinghua Zhang, Gang Cai, Hailong Wang, Jun Huang, Xuefeng Chen
Summary: The acetylation and deacetylation of RPA are crucial for regulating its function in DNA replication and repair processes. RPA is acetylated by NuA4 upon DNA damage, and mutations in RPA acetylation lead to spontaneous mutations and impaired DNA repair. Proper acetylation and deacetylation of RPA are necessary for its normal nuclear localization and ssDNA binding ability. These findings suggest that timely acetylation and deacetylation of RPA are conserved mechanisms promoting high-fidelity replication and repair in eukaryotes.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
David G. Nickens, Matthew L. Bochman
Summary: Pif1 helicase plays a critical role in DNA metabolism, relying on DNA binding and ATP hydrolysis to unwind DNA. Studies have shown that Pif1 preferentially binds to structured G-rich single-stranded DNA, but its preferred binding substrates do not maximally stimulate ATP hydrolysis activity.
Article
Genetics & Heredity
Andrew Ziesel, Qixuan Weng, Jasvinder S. Ahuja, Abhishek Bhattacharya, Raunak Dutta, Evan Cheng, G. Valentin Borner, Michael Lichten, Nancy M. Hollingsworth
Summary: During meiosis, recombination between homologous chromosomes generates crossovers that promote proper segregation. Recombination is initiated by Spo11-catalyzed DNA double strand breaks. Rad51 and Dmc1 bind to single strand tails to form presynaptic filaments, mediate strand invasion and generate D-loops. D-loop processing forms crossover and noncrossover recombinants. Meiotic recombination occurs in two phases: Rad51 is inhibited in Phase 1 and Dmc1 mediates interhomolog recombination, while Rad51 becomes active in Phase 2 and functions with Rad54 to repair residual DSBs, making increasing use of sister chromatids. The transition from Phase 1 to Phase 2 is controlled by the meiotic recombination checkpoint. Constitutive activation of Rad51 in Phase 1 leads to delay in meiotic recombination and increases chromosome nondisjunction.