Article
Multidisciplinary Sciences
Jeremy Sandoz, Max Cigrang, Amelie Zachayus, Philippe Catez, Lise-Marie Donnio, Clemence Elly, Jadwiga Nieminuszczy, Pietro Berico, Cathy Braun, Sergey Alekseev, Jean-Marc Egly, Wojciech Niedzwiedz, Giuseppina Giglia-Mari, Emmanuel Compe, Frederic Coin
Summary: The exonuclease EXD2 plays a role in the recovery of class II gene transcription after UV irradiation. It moves from mitochondria to the nucleus where it interacts with RNA Pol II and degrades newly synthesized mRNA, allowing transcription to resume after DNA repair. Lack of EXD2 impairs mRNA synthesis recovery and reduces cell survival after UV irradiation, but does not affect DNA repair. Overexpression of wild-type EXD2 restores mRNA synthesis recovery and cell survival. EXD2 is relocated from mitochondria to the nucleus upon UV irradiation, where it interacts transiently with chromatin-bound RNA Pol II to promote the degradation of nascent mRNAs. In vitro experiments show that EXD2 primarily interacts with elongation-blocked RNA Pol II and efficiently degrades mRNA. Overall, this study highlights the crucial role of EXD2 in the transcriptional response to genotoxic attack, where it interacts with elongation-stalled RNA Pol II on chromatin to potentially degrade the associated nascent mRNA, allowing transcription restart after DNA repair.
NATURE COMMUNICATIONS
(2023)
Article
Oncology
Shuo Wang, Guillaume C. Onyeaghala, Nathan Pankratz, Heather H. Nelson, Bharat Thyagarajan, Weihong Tang, Faye L. Norby, Chinenye Ugoji, Corinne E. Joshu, Christian R. Gomez, David J. Couper, Josef Coresh, Elizabeth A. Platz, Anna E. Prizment
Summary: The study found that MICA and MICB are associated with colorectal cancer development, and low sMICA levels are related to lower risk of colorectal cancer. These findings highlight the importance of immune surveillance in colorectal cancer.
CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
(2023)
Article
Biochemistry & Molecular Biology
Yanping Tang, Yanan Fan, Qing Luo, Guanbin Song
Summary: In this study, we investigated the effect of pressure loading on human hepatocytes and found that it leads to DNA damage, cell cycle arrest, and activation of the DNA damage response. We also discovered that pressure loading upregulates Dicer expression and activates the ERK1/2 signaling pathway. Our findings suggest that compressive stress loading induces hepatocyte DNA damage through the ERK1/2-Dicer signaling pathway, providing evidence for a better understanding of the link between altered mechanical environment and liver diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Zied Boudhraa, Kossay Zaoui, Hubert Fleury, Maxime Cahuzac, Sophie Gilbert, Guergana Tchakarska, Jennifer Kendall-Dupont, Euridice Carmona, Diane Provencher, Anne-Marie Mes-Masson
Summary: The study demonstrates a new approach to target epithelial ovarian cancer survival by inhibiting Ran. There is an inverse correlation between Ran and NR1D1, playing a crucial role in aneuploid cells. Ran affects DNA repair pathways by destabilizing NR1D1 mRNA through miR4472 interference.
Article
Oncology
Amr Ghaleb, Lucia Roa, Natalia Marchenko
Summary: The biological consequences of low-dose radiation (LDR) in breast cancer are unclear, while high-dose radiation (HDR) promotes DNA repair and cell cycle arrest. Mutant p53 promotes mammary tumorigenesis following LDR, but has negligible effects on tumors carrying the wild-type p53 allele.
Article
Environmental Sciences
Shuwei Yao, Xintong Chen, Ningdong Hu, Nan Zhang, Miaoyun Qiu, Yangyang Jia, Han Zhang, Jihuan Liang, Zehao Chen, Liting Zheng, Jialu Zhu, Rulin Mao, Yiguo Jiang
Summary: In this study, it was found that the environmental pollutant benzo[a]pyrene (B[a]P) upregulated the expression of circular RNA circ_0003552 through m6A modification, leading to DNA damage. These findings revealed the key role of epigenetics in carcinogen-induced DNA damage and suggested that quantifiable changes in circ_0003552 expression could serve as an early biomarker for genetic-related diseases.
ENVIRONMENTAL POLLUTION
(2023)
Review
Oncology
Caroline Molinaro, Alain Martoriati, Katia Cailliau
Summary: Cells respond to genotoxic stress through complex protein pathways called DNA damage response (DDR), ensuring genomic integrity and activating processes like DNA repair, cell cycle regulation, and programmed cell death. Alterations in DDR network proteins can lead to various diseases, including cancer. Recent technological advancements have allowed for the exploitation of DDR vulnerabilities to improve cancer treatments through DNA damage strategies and combination therapies.
Article
Pharmacology & Pharmacy
Liyu Jiang, Yan Zeng, Leilei Ai, Hao Yan, Xiaochun Yang, Peihua Luo, Bo Yang, Zhifei Xu, Qiaojun He
Summary: The application of lapatinib, a dual inhibitor, is limited by its cutaneous toxicity. This study revealed that lapatinib-induced cutaneous toxicity is associated with mitochondrial dysfunction, DNA damage, apoptosis of keratinocytes, aberrant immune response, and release of inflammatory factors. Downregulated expression of the DNA repair protein HMGB1 played a critical role in these toxic reactions. Restoring HMGB1 expression might be an effective remedy for lapatinib-induced cutaneous toxicity. Additionally, saikosaponin A could rescue reduced HMGB1 transcription and alleviate lapatinib-induced DNA damage, keratinocyte apoptosis, and toxicity in mice.
BIOCHEMICAL PHARMACOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Alia dos Santos, Christopher P. Toseland
Summary: The nucleus in eukaryotic cells houses the cell's genomic material. Factors like chromatin structure and the nuclear lamina play essential roles in the mechanical properties of the nucleus. Nuclear stiffness impacts and is impacted by cellular processes such as DNA damage and repair.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Hematology
Effie W. Petersdorf, Caroline McKallor, Mari Malkki, Meilun He, Stephen R. Spellman, Katharine C. Hsu, Roland K. Strong, Ted Gooley, Phil Stevenson
Summary: Gene variation of NKG2D receptor and its ligands MICA and MICB can affect relapse and survival after transplantation, providing insights for predicting transplantation failure.
Article
Oncology
Harry Scherthan, Stephanie-Quinta Wagner, Jan Grundhoefer, Nicole Matejka, Jessica Mueller, Steffen Mueller, Sarah Rudigkeit, Matthias Sammer, Sarah Schoof, Matthias Port, Judith Reindl
Summary: Proton minibeam radiotherapy (pMBRT) can achieve tissue-sparing effects at the sub-cellular level, reducing side effects to the skin, and successfully repairing DNA damage.
Article
Medicine, Research & Experimental
Liwei An, Zhifa Cao, Pingping Nie, Hui Zhang, Zhenzhu Tong, Fan Chen, Yang Tang, Yi Han, Wenjia Wang, Zhangting Zhao, Qingya Zhao, Yuqin Yang, Yuanzhi Xu, Gemin Fang, Lei Shi, Huixiong Xu, Haiqing Ma, Shi Jiao, Zhaocai Zhou
Summary: We identified the Hippo-STRIPAK complex as a crucial regulator of DNA double-stranded break (DSB) repair and genomic stability. Inhibition of STRIPAK-mediated MST1/2 activation increased the DSB repair capacity of cancer cells and conferred resistance to radio- and chemotherapy and PARP inhibition. Furthermore, targeting the STRIPAK assembly effectively restored the kinase activity of MST1/2 and resensitized cancer cells to PARP inhibitors. Our findings suggest a previously unrecognized role for STRIPAK in modulating DSB repair and provide translational implications for a new type of synthetic lethality anticancer therapy by cotargeting STRIPAK and PARP.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
Article
Biochemistry & Molecular Biology
Marco Klanschnig, Monika Cserjan-Puschmann, Gerald Striedner, Reingard Grabherr
Summary: A new CRISPRa construct, named SMS, was discovered, which combines the PAM independent Cas9 variant SpRY with phage protein MCP fused to transcriptional activator SoxS. It can accurately up-regulate endogenous genes in bacteria and control transgenes at non-NGG PAM sites.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Multidisciplinary Sciences
Lorna S. Thorne, Garret Rochford, Timothy D. Williams, Andrew D. Southam, Giovanny Rodriguez-Blanco, Warwick B. Dunn, Nikolas J. Hodges
Summary: Cytoglobin plays a crucial role in the progression of oral squamous cell carcinoma by mediating changes in gene expression related to stress response and metabolism, protecting cells from cisplatin-induced apoptosis and oxidative stress. Lipidomic analysis revealed up-regulation of cardiolipin in cells expressing cytoglobin, suggesting a potential mechanism for cancer cells to exploit phenotypic changes and facilitate disease progression.
SCIENTIFIC REPORTS
(2021)
Article
Oncology
Shuai Ma, Jieyou Zhang, Qiushi Guo, Cheng Cao, Kaiwen Bao, Ling Liu, Charlie Degui Chen, Zhe Liu, Jie Yang, Na Yang, Zhi Yao, Lei Shi
Summary: The dysregulation of the PHF8-TOPBP1 signaling pathway is involved in breast tumorigenesis and patient survival. Disruption of this pathway suppresses breast tumor growth and increases sensitivity to PARP inhibitors and platinum drugs.
Article
Biochemistry & Molecular Biology
Pei-Ying Zhang, Guiling Li, Zhu-Jun Deng, Li-Yuan Liu, Li Chen, Jun-Zhou Tang, Yu-Qun Wang, Su-Ting Cao, Yu-Xiao Fang, Fuping Wen, Yunsheng Xu, Xiaoming Chen, Ke-Qing Shi, Wen-Feng Li, Congying Xie, Kai-Fu Tang
NUCLEIC ACIDS RESEARCH
(2016)
Article
Biochemistry & Molecular Biology
D. Ma, X. Chen, P-Y Zhang, H. Zhang, L-J Wei, S. Hu, J-Z Tang, M-T Zhou, C. Xie, R. Ou, Y. Xu, K-F Tang
Article
Oncology
Meng-Tao Zhou, Chunming Zhao, Xiao Chen, Heng-Chao Zhang, Guiling Li, Hongyan Lou, Wen-Jie Huang, Lin-Jie Wei, De-Wei Li, Xiaoli Wu, Zhe-Chao Zhang, Hui Liu, Rongying Ou, Wen-Jun Yang, Shanshan Hu, Yunsheng Xu, Kai-Fu Tang
Review
Pharmacology & Pharmacy
Yiyi Lu, Fengxing Tao, Meng-Tao Zhou, Kai-Fu Tang
PHARMACOLOGICAL RESEARCH
(2019)
Article
Cell Biology
Yao Liu, Xiao Chen, Yuemei Zhao, Xing-Yue Wang, Yu-Wei Luo, Lina Chen, Weiyun Wang, Shouhui Zhong, Meizhen Hu, Zhizheng Dai, Jiayu Jiang, Xin Wang, Hongyu Ji, Xiao-Xiao Cheng, Anqi Zheng, Jiwei Zuo, Hui Liu, Di Ma, Zhicheng Luo, Fang Cao, Shanshan Hu, Ai-Long Huang, Kai-Fu Tang
Summary: A class of small cytosolic dsDNA molecules, around 20-40 bp in length, have been found to compete with long dsDNA for binding to cGAS, inhibiting cGAS activation and inflammation. These small DNA molecules promote the interaction between cGAS and Beclin-1, releasing Rubicon, which negatively regulates PI3KC3, from the Beclin-1-PI3KC3 complex. This leads to PI3KC3 activation, inducing autophagy and degradation of STING and long dsDNA. The discovery has therapeutic implications for cytosolic DNA-associated inflammatory diseases.
Article
Medicine, Research & Experimental
Xiaoli Wu, Xiao Chen, Hui Liu, Zhong-Wei He, Zheng Wang, Lin-Jie Wei, Wei-Yun Wang, Shouhui Zhong, Qin He, Zhechao Zhang, Rongying Ou, Jian Gao, Youchun Lei, Wenjun Yang, Guanbin Song, Yi Jin, Lingli Zhou, Yunsheng Xu, Kai-Fu Tang
Article
Biotechnology & Applied Microbiology
Xiao Chen, Mi Liu, Hongyan Lou, Yiyi Lu, Meng-Tao Zhou, Rongying Ou, Yunsheng Xu, Kai-Fu Tang
Article
Oncology
Xiao Chen, Wen-Feng Li, Xiaoli Wu, Heng-Chao Zhang, Li Chen, Pei-Ying Zhang, Li-Yuan Liu, Di Ma, Tongke Chen, Lingli Zhou, Yunsheng Xu, Meng-Tao Zhou, Kai-Fu Tang
