keyword
https://read.qxmd.com/read/38424264/excavatolide-c-cisplatin-combination-induces-antiproliferation-and-drives-apoptosis-and-dna-damage-in-bladder-cancer-cells
#21
JOURNAL ARTICLE
Tsu-Ming Chien, Che-Wei Yang, Chia-Hung Yen, Bi-Wen Yeh, Wen-Jeng Wu, Jyh-Horng Sheu, Hsueh-Wei Chang
Excavatolide C (EXCC), a marine coral-derived compound, exhibits an antiproliferation effect on bladder cancer cells. The present study evaluated the improvement in the antiproliferation ability of EXCC by co-treatment with cisplatin in bladder cancer cells. EXCC/cisplatin (12.5 and 1 μg/mL) showed higher antiproliferation effects on bladder cancer cells than single treatments (EXCC or cisplatin alone) in the 48 h ATP assay. EXCC/cisplatin also enhanced the increase in subG1, annexin V-mediated apoptosis, and activation of poly (ADP-ribose) polymerase (PARP) and several caspases (caspases 3, 8, and 9) compared to the single treatments...
February 29, 2024: Archives of Toxicology
https://read.qxmd.com/read/38423600/non-homologous-end-joining-genotype-mrna-expression-and-dna-repair-capacity-in-childhood-acute-lymphocytic-leukemia
#22
JOURNAL ARTICLE
Chao-Chun Chen, Wen-Shin Chang, Jen-Sheng Pei, Chien-Chung Kuo, Chung-Hsing Wang, Yun-Chi Wang, Pei-Chen Hsu, Jie-Long He, Jian Gu, DA-Tian Bau, Chia-Wen Tsai
BACKGROUND/AIM: The capacity for non-homologous end-joining (NHEJ) repair plays a pivotal role in maintaining genome stability and in carcinogenesis. However, there is little literature on the involvement of NHEJ-related genes in childhood acute lymphocytic leukemia (ALL). Our study aimed to elucidate the impact of polymorphisms of X-ray repair cross-complementing group 4 (XRCC4) (rs6869366, rs2075685, rs2075686, rs28360071, rs3734091, rs28360317, rs1805377), XRCC5 (rs828907, rs11685387, rs9288518), XRCC6 (rs5751129, rs2267437, rs132770, rs132774), XRCC7 rs7003908, and DNA ligase IV (LIG4) rs1805388, on the odds of childhood ALL...
2024: Cancer Genomics & Proteomics
https://read.qxmd.com/read/38423014/a-di-acetyl-decorated-chromatin-signature-couples-liquid-condensation-to-suppress-dna-end-synapsis
#23
JOURNAL ARTICLE
Kaiwen Bao, Yanhui Ma, Yuan Li, Xilin Shen, Jiao Zhao, Shanshan Tian, Chunyong Zhang, Can Liang, Ziyan Zhao, Ying Yang, Kai Zhang, Na Yang, Fei-Long Meng, Jihui Hao, Jie Yang, Tao Liu, Zhi Yao, Ding Ai, Lei Shi
Appropriate DNA end synapsis, regulated by core components of the synaptic complex including KU70-KU80, LIG4, XRCC4, and XLF, is central to non-homologous end joining (NHEJ) repair of chromatinized DNA double-strand breaks (DSBs). However, it remains enigmatic whether chromatin modifications can influence the formation of NHEJ synaptic complex at DNA ends, and if so, how this is achieved. Here, we report that the mitotic deacetylase complex (MiDAC) serves as a key regulator of DNA end synapsis during NHEJ repair in mammalian cells...
February 21, 2024: Molecular Cell
https://read.qxmd.com/read/38412274/dna-pkcs-suppresses-illegitimate-chromosome-rearrangements
#24
JOURNAL ARTICLE
Jinglong Wang, Cheyenne A Sadeghi, Richard L Frock
Two DNA repair pathways, non-homologous end joining (NHEJ) and alternative end joining (A-EJ), are involved in V(D)J recombination and chromosome translocation. Previous studies reported distinct repair mechanisms for chromosome translocation, with NHEJ involved in humans and A-EJ in mice predominantly. NHEJ depends on DNA-PKcs, a critical partner in synapsis formation and downstream component activation. While DNA-PKcs inhibition promotes chromosome translocations harboring microhomologies in mice, its synonymous effect in humans is not known...
February 27, 2024: Nucleic Acids Research
https://read.qxmd.com/read/38412240/lc3b-drives-transcription-associated-homologous-recombination-via-direct-interaction-with-r-loops
#25
JOURNAL ARTICLE
Junghyun Yoon, Yiseul Hwang, Hansol Yun, Jee Min Chung, Soyeon Kim, Gyeongmin Kim, Yeji Lee, Byoung Dae Lee, Ho Chul Kang
Exploring the connection between ubiquitin-like modifiers (ULMs) and the DNA damage response (DDR), we employed several advanced DNA damage and repair assay techniques and identified a crucial role for LC3B. Notably, its RNA recognition motif (RRM) plays a pivotal role in the context of transcription-associated homologous recombination (HR) repair (TA-HRR), a particular subset of HRR pathways. Surprisingly, independent of autophagy flux, LC3B interacts directly with R-loops at DNA lesions within transcriptionally active sites via its RRM, promoting TA-HRR...
February 27, 2024: Nucleic Acids Research
https://read.qxmd.com/read/38411120/the-dcas9-based-genome-editing-in-plasmodium-yoelii
#26
JOURNAL ARTICLE
Chao Zhang, Shijie Yang, Elvis Quansah, Ziyu Zhang, Weiran Da, Bingjie Wang
Genetic editing is a powerful tool for functional characterization of genes in various organisms. With its simplicity and specificity, the CRISPR-Cas9 technology has become a popular editing tool, which introduces site-specific DNA double-strand breaks (DSBs), and then leverages the endogenous repair pathway for DSB repair via homology-directed repair (HDR) or the more error-prone non-homologous end joining (NHEJ) pathways. However, in the Plasmodium parasites, the lack of a typical NHEJ pathway selects for DSB repair through the HDR pathway when a homologous DNA template is available...
February 27, 2024: MSphere
https://read.qxmd.com/read/38407308/dna-pk-controls-apollo-s-access-to-leading-end-telomeres
#27
JOURNAL ARTICLE
Ceylan Sonmez, Beatrice Toia, Patrik Eickhoff, Andreea Medeea Matei, Michael El Beyrouthy, Björn Wallner, Max E Douglas, Titia de Lange, Francisca Lottersberger
The complex formed by Ku70/80 and DNA-PKcs (DNA-PK) promotes the synapsis and the joining of double strand breaks (DSBs) during canonical non-homologous end joining (c-NHEJ). In c-NHEJ during V(D)J recombination, DNA-PK promotes the processing of the ends and the opening of the DNA hairpins by recruiting and/or activating the nuclease Artemis/DCLRE1C/SNM1C. Paradoxically, DNA-PK is also required to prevent the fusions of newly replicated leading-end telomeres. Here, we describe the role for DNA-PK in controlling Apollo/DCLRE1B/SNM1B, the nuclease that resects leading-end telomeres...
February 26, 2024: Nucleic Acids Research
https://read.qxmd.com/read/38396904/dna-double-strand-break-and-response-fluorescent-assays-choices-and-interpretation
#28
REVIEW
Jake Atkinson, Eva Bezak, Hien Le, Ivan Kempson
Accurately characterizing DNA double-stranded breaks (DSBs) and understanding the DNA damage response (DDR) is crucial for assessing cellular genotoxicity, maintaining genomic integrity, and advancing gene editing technologies. Immunofluorescence-based techniques have proven to be invaluable for quantifying and visualizing DSB repair, providing valuable insights into cellular repair processes. However, the selection of appropriate markers for analysis can be challenging due to the intricate nature of DSB repair mechanisms, often leading to ambiguous interpretations...
February 13, 2024: International Journal of Molecular Sciences
https://read.qxmd.com/read/38396618/crispr-ribonucleoprotein-mediated-precise-editing-of-multiple-genes-in-porcine-fibroblasts
#29
JOURNAL ARTICLE
Xiaochen Guo, Chang Liu, Yunjing Zhao, Chaoqian Jiang, Junxue Jin, Zhonghua Liu, Yanshuang Mu
The multi-gene editing porcine cell model can analyze the genetic mechanisms of multiple genes, which is beneficial for accelerating genetic breeding. However, there has been a lack of an effective strategy to simultaneously perform precise multi-gene editing in porcine cells. In this study, we aimed to improve the efficiency of CRISPR RNP-mediated precise gene editing in porcine cells. CRISPR RNP, including Cas9 protein, sgRNA, and ssODN, was used to generate precise nucleotide substitutions by homology-directed repair (HDR) in porcine fetal fibroblasts (PFFs)...
February 18, 2024: Animals: An Open Access Journal From MDPI
https://read.qxmd.com/read/38383726/the-bap1-nuclear-deubiquitinase-is-involved-in-the-nonhomologous-end-joining-pathway-of-double-strand-dna-repair-through-interaction-with-dna-pk
#30
JOURNAL ARTICLE
Hiroki Sato, Tatsuo Ito, Takuo Hayashi, Shigehisa Kitano, Hediye Erdjument-Bromage, Matthew J Bott, Shinichi Toyooka, Marjorie Zauderer, Marc Ladanyi
BRCA1-associated protein 1 (BAP1) has emerged as a major tumor suppressor gene in diverse cancer types, notably in malignant pleural mesothelioma (DPM), and has also been identified as a germline cancer predisposition gene for DPM and other select cancers. However, its role in the response to DNA damage has remained unclear. Here, we show that BAP1 inactivation is associated with increased DNA damage both in Met-5A human mesothelial cells and human DPM cell lines. Through proteomic analyses, we identified PRKDC as an interaction partner of BAP1 protein complexes in DPM cells and 293 T human embryonic kidney cells...
February 21, 2024: Oncogene
https://read.qxmd.com/read/38380364/selective-inhibition-of-dna-ligase-iv-provides-additional-efficacy-to-the-treatment-of-anaplastic-thyroid-cancer
#31
JOURNAL ARTICLE
Sathya Neelature Sriramareddy, Majeed Jamakhani, Léa Vilanova, Hélène Brossel, Bernard Staumont, Malik Hamaidia
BACKGROUND: Although the incidence of anaplastic thyroid carcinoma (ATC) is low (2.5% of thyroid cancer cases), this cancer has a very poor prognosis (survival rates < 5 months) and accounts for 14-39% of deaths. Conventional therapies based on surgery in combination with radiotherapy or chemotherapy showed limited effectiveness primarily due to the robust and protective DNA damage response in thyroid cancer cells. METHODS: We used single-cell transcriptomic data from patients with different subtypes of thyroid cancer to study expression of genes involved in homologous recombination (HR) and non-homologous end joining (NHEJ) pathways...
2024: Frontiers in Oncology
https://read.qxmd.com/read/38376092/improving-homology-directed-repair-by-small-molecule-agents-for-genetic-engineering-in-unconventional-yeast-learning-from-the-engineering-of-mammalian-systems
#32
REVIEW
Min Lu, Sonja Billerbeck
The ability to precisely edit genomes by deleting or adding genetic information enables the study of biological functions and the building of efficient cell factories. In many unconventional yeasts, such as those promising new hosts for cell factory design but also human pathogenic yeasts and food spoilers, this progress has been limited by the fact that most yeasts favour non-homologous end joining (NHEJ) over homologous recombination (HR) as a DNA repair mechanism, impairing genetic access to these hosts...
February 2024: Microbial Biotechnology
https://read.qxmd.com/read/38374229/fsp1-inhibition-enhances-olaparib-sensitivity-in-brca-proficient-ovarian-cancer-patients-via-a-nonferroptosis-mechanism
#33
JOURNAL ARTICLE
Huixian Miao, Huangyang Meng, Yashuang Zhang, Tian Chen, Lin Zhang, Wenjun Cheng
Poly ADP-ribose polymerase inhibitors (PARPis) exhibit promising efficacy in patients with BRCA mutations or homologous repair deficiency (HRD) in ovarian cancer (OC). However, less than 40% of patients have HRD, it is vital to expand the indications for PARPis in BRCA-proficient patients. Ferroptosis suppressor protein 1 (FSP1) is a key protein in a newly identified ferroptosis-protective mechanism that occurs in parallel with the GPX4-mediated pathway and is associated with chemoresistance in several cancers...
February 19, 2024: Cell Death and Differentiation
https://read.qxmd.com/read/38373114/t-circle-vector-strategy-increases-nhej-mediated-site-specific-integration-in-soybean
#34
JOURNAL ARTICLE
Xudong Ye, John Bradley, Larry Gilbertson
No abstract text is available yet for this article.
February 19, 2024: Plant Biotechnology Journal
https://read.qxmd.com/read/38372363/analysis-of-nonhomologous-end-joining-and-homologous-recombination-efficiency-in-hek-293t-cells-using-gfp-based-reporter-systems
#35
JOURNAL ARTICLE
Lu-Ping Zhang, Yong-Hong Nie, Tuo Tang, Ai-Xue Zheng, Xian Hong, Tao Wang
DNA double-strand breaks (DSBs) represent the most perilous DNA lesions, capable of inducing substantial genetic information loss and cellular demise. In response, cells employ two primary mechanisms for DSB repair: nonhomologous end joining (NHEJ) and homologous recombination (HR). Quantifying the efficiency of NHEJ and HR separately is crucial for exploring the relevant mechanisms and factors associated with each. The NHEJ assay and HR assay are established methods used to measure the efficiency of their respective repair pathways...
February 2, 2024: Journal of Visualized Experiments: JoVE
https://read.qxmd.com/read/38360689/genome-scale-transcriptional-activation-by-non-homologous-end-joining-mediated-integration-in-yarrowia-lipolytica
#36
JOURNAL ARTICLE
Xiaoqin Liu, Jingyu Deng, Jinhong Zhang, Zhiyong Cui, Qingsheng Qi, Jin Hou
BACKGROUND: Genome-scale screening can be applied to efficiently mine for unknown genes with phenotypes of interest or special functions. It is also useful to identify new targets for engineering desirable properties of cell factories. RESULTS: Here, we designed a new approach for genome-scale transcription activation using non-homologous end joining (NHEJ)-mediated integration in Yarrowia lipolytica. We utilized this approach to screen for genes that, upon activation, confer phenotypes including improved acetic acid tolerance and xylose metabolism...
February 15, 2024: Biotechnol Biofuels Bioprod
https://read.qxmd.com/read/38359981/quantitative-analysis-of-nuclear-deformations-and-dna-damage-foci-dynamics-by-live-cell-imaging
#37
JOURNAL ARTICLE
Elena Faustini, Andrea Panza, Matteo Longaretti, Francisca Lottersberger
The correct repair of DNA Double Strand Breaks (DSBs) is fundamental to prevent the loss of genetic information, mutations, and chromosome rearrangements. An emerging determinant of DNA repair is chromatin mobility. However, how chromatin mobility can influence DSBs repair is still poorly understood. While increased mobility is generally associated with the correct repair by Homologous Recombination (HR) of DSBs generated in heterochromatin, it promotes the mis-repair of multiple distal DSBs by Non-Homologous End Joining (NHEJ)...
2024: Methods in Cell Biology
https://read.qxmd.com/read/38353495/deposition-of-onco-histone-h3-3-g34w-leads-to-dna-repair-deficiency-and-activates-cgas-sting-mediated-immune-responses
#38
JOURNAL ARTICLE
Daniela Mancarella, Henrik Ellinghaus, Gianluca Sigismondo, Olivera Veselinov, Alexander Kühn, Ashish Goyal, Mark Hartmann, Jörg Fellenberg, Jeroen Krijgsveld, Christoph Plass, Odilia Popanda, Peter Schmezer, Ali Bakr
Mutations in histone H3.3-encoding genes causing mutant histone tails are associated with specific cancers such as pediatric glioblastomas (H3.3-G34R/V) and giant cell tumor of the bone (H3.3-G34W). The mechanisms by which these mutations promote malignancy are not completely understood. Here we show that cells expressing H3.3-G34W exhibit DNA double-strand breaks (DSBs) repair defects and increased cellular sensitivity to ionizing radiation (IR). Mechanistically, H3.3-G34W can be deposited to damaged chromatin, but in contrast to wild-type H3...
February 14, 2024: International Journal of Cancer. Journal International du Cancer
https://read.qxmd.com/read/38344908/acetylcholine-esterase-of-drosophila-melanogaster-a-laboratory-model-to-explore-insecticide-susceptibility-gene-drives
#39
JOURNAL ARTICLE
Natalia Hernandes, Xiaomeng Mollyann Qi, Soumitra Bhide, Courtney Brown, Benjamin J Camm, Simon W Baxter, Charles Robin
BACKGROUND: One of the proposed applications of gene drives has been to revert pesticide resistant mutations back to the ancestral susceptible state. Insecticides that have become ineffective because of the rise of resistance could have reinvigorated utility and be used to suppress pest populations again, perhaps at lower application doses. RESULTS: We have created a laboratory model for susceptibility gene drives that replaces field-selected resistant variants of the acetylcholine esterase (Ace) locus of Drosophila melanogaster with ancestral susceptible variants...
February 12, 2024: Pest Management Science
https://read.qxmd.com/read/38341432/structural-role-for-dna-ligase-iv-in-promoting-the-fidelity-of-non-homologous-end-joining
#40
JOURNAL ARTICLE
Benjamin M Stinson, Sean M Carney, Johannes C Walter, Joseph J Loparo
Nonhomologous end joining (NHEJ), the primary pathway of vertebrate DNA double-strand-break (DSB) repair, directly re-ligates broken DNA ends. Damaged DSB ends that cannot be immediately re-ligated are modified by NHEJ processing enzymes, including error-prone polymerases and nucleases, to enable ligation. However, DSB ends that are initially compatible for re-ligation are typically joined without end processing. As both ligation and end processing occur in the short-range (SR) synaptic complex that closely aligns DNA ends, it remains unclear how ligation of compatible ends is prioritized over end processing...
February 10, 2024: Nature Communications
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