Article
Biochemistry & Molecular Biology
Jae Jin Kim, Seo Yun Lee, Yiseul Hwang, Soyeon Kim, Jee Min Chung, Sangwook Park, Junghyun Yoon, Hansol Yun, Jae-Hoon Ji, Sunyoung Chae, Hyeseong Cho, Chan Gil Kim, Ted M. Dawson, Hongtae Kim, Valina L. Dawson, Ho Chul Kang
Summary: Mutual crosstalk among PAR, PARP1 metabolites, and DNA repair machinery is a key regulatory mechanism of DDR. USP39, identified as an inactive DUB associated with PAR-coupled DDR, localizes to DNA lesions in a PAR-dependent manner, regulating NHEJ and liquid demixing. Additionally, the USP39-associated spliceosome complex controls homologous recombination repair in a PAR-independent manner.
NUCLEIC ACIDS RESEARCH
(2021)
Review
Genetics & Heredity
Charlotte Audoynaud, Stephan Vagner, Sarah Lambert
Summary: RNAs and associated proteins, including RNA binding proteins, may regulate NHEJ during DNA replication to sustain genome stability.
TRENDS IN GENETICS
(2021)
Article
Biochemistry & Molecular Biology
Chia-Wen Tsai, Liang-Chun Shih, Wen-Shin Chang, Che-Lun Hsu, Jie-Long He, Te-Chun Hsia, Yun-Chi Wang, Jian Gu, Da-Tian Bau
Summary: Defects in the non-homologous end-joining (NHEJ) DNA repair pathway increase the risk of nasopharyngeal carcinoma (NPC). This study aimed to investigate the contribution of NHEJ genotypes to NPC risk. The results showed that certain genetic variants in XRCC4 and XRCC6 were associated with increased NPC susceptibility. Additionally, XRCC6 rs2267437 was found to influence mRNA and protein expression levels, as well as the NHEJ repair capacity.
Article
Plant Sciences
Meiyang Chen, Erdi Zhao, Minjing Li, Ming Xu, Shiyu Hao, Yingli Gao, Xingli Wu, Xiang Li, Yue Yu, Zhenhai Yu, Yancun Yin
Summary: The study aimed to evaluate the efficacy of kaempferol (Kae), a flavonoid, in treating human glioma and its mechanism in regulating DNA repair. The results showed that Kae significantly inhibits the viability and proliferation of glioma cells, and induces the accumulation of DNA double-strand breaks (DSBs) by suppressing non-homologous end joining (NHEJ) repair. In an orthotopic transplantation model, Kae also exhibited significant inhibition of glioma growth. These findings suggest that inhibiting the release of Ku80 from DSBs by Kae may be an effective approach for glioma treatment.
Article
Oncology
Min-Ji Yoon, Hwijae Cha, Jungho Ahn, Danbi Lee, Hyun-Seok Jeong, Hwa Seon Koo, Youn-Jung Kang
Summary: Ovarian cancer is the deadliest gynecological malignancy worldwide, and resistance to genotoxic stress may be a critical cause of chemoresistance in patients.
Article
Toxicology
Huixian Zeng, Meizhen Li, Qiuhan Hua, Yufei Liu, Yueting Shao, Qinqin Diao, Yihui Ling, Han Zhang, Miaoyun Qiu, Jialu Zhu, Xun Li, Rong Zhang, Yiguo Jiang
Summary: The study revealed that exposure to PM2.5 resulted in histopathological changes and DNA damage in the lung, kidney, and spleen of mice, decreased cell viability, and increased DNA damage. The upregulation of circ_Cabin1 after PM2.5 exposure inhibited NHEJ repair.
ARCHIVES OF TOXICOLOGY
(2021)
Article
Multidisciplinary Sciences
Zhuoyi Liang, Vipul Kumar, Marie Le Bouteiller, Jeffrey Zurita, Josefin Kenrick, Sherry G. Lin, Jiangman Lou, Jianqiao Hu, Adam Yongxin Ye, Cristian Boboila, Frederick W. Alt, Richard L. Frock
Summary: The study demonstrates that in Lig4-deficient G1-arrested progenitor B cells, Ku-dependent blockage of A-EJ leads to functional endjoining suppression. However, joining of RAG-generated DSBs in Ku70-deficient or Ku70/Lig4 double-deficient cells occurs through a translocation-like A-EJ mechanism.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
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
Oncology
Daniele Caracciolo, Caterina Riillo, Maria Teresa Di Martino, Pierosandro Tagliaferri, Pierfrancesco Tassone
Summary: Cancer onset and progression result in high levels of DNA damage, with error-prone DNA repair pathways promoting genomic instability that leads to the appearance of cancer hallmarks through progressive genetic aberrations in tumor cells. This provides a potential target for precision oncology through the inhibition of Alternative Non-Homologous End Joining (Alt-NHEJ) as a new cancer vulnerability.
Article
Microbiology
Kwang-Woo Jung, Jong-Hyun Jung, Ha-Young Park
Summary: This study reveals that under genotoxic stress, Rad51-mediated homologous recombination (HR) and Ku70/Ku80-mediated non-homologous end joining (NHEJ) play crucial roles in regulating DNA damage response and maintaining genome stability in the radiation-resistant fungus Cryptococcus neoformans.
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
Multidisciplinary Sciences
Sophie Cowman, Barry Pizer, Violaine See
Summary: This study investigated the impact of chronic hypoxia on DNA repair gene expression in glioblastoma cell lines, revealing that hypoxia primarily resulted in downregulation of DNA repair genes, with the extent of downregulation depending on the severity of hypoxia. Some downregulations were directly controlled by HIF activity, indicating that multiple molecular mechanisms are involved in hypoxia-induced reprogramming of DNA repair gene transcription.
Article
Environmental Sciences
Ling Liu, Jinjin Cui, Shijie Chen, Xia Zhang, Suhua Wang, Lihua Huang
Summary: In this study, NPs-Nd2O3 exposure was found to induce DNA damage and down-regulate circ_002363 levels in human bronchial epithelial cells and rat lung tissue. Functional experiments demonstrated that circ_002363 acts as a regulator of DNA damage by interacting with proteins involved in the NHEJ DNA repair pathway. The formation of circ_002363 was found to be regulated by the RNA binding protein BCAS2. These findings provide new insights into the regulatory mechanisms of circular RNAs and the relationship between genetics and epigenetics in the development of diseases following exposure to environmental chemicals.
SCIENCE OF THE TOTAL ENVIRONMENT
(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
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.