Article
Multidisciplinary Sciences
Jimin Li, Jingyu Zhao, Xiaoli Gan, Yanyan Wang, Donghao Jiang, Liang Chen, Fangwei Wang, Jingyan Xu, Huadong Pei, Jun Huang, Xuefeng Chen
Summary: The interaction between the single-strand DNA-binding factor Replication protein A (RPA) and Ring finger protein 20 (RNF20) is important for chromosome segregation and DNA repair. RPA recruits RNF20 to mitotic centromeres and chromosomal breaks, leading to proper loading of repair proteins and maintenance of genome stability. The RPA-RNF20-SNF2H cascade plays a crucial role in preserving genome stability by coupling histone modification to chromosome segregation and DNA repair.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Multidisciplinary Sciences
Xuejie Wang, Yang Dong, Xiaocong Zhao, Jinbao Li, Jordan Lee, Zhenxin Yan, Shuangshuang Yang, Wenqiang Wu, Ximiao Hou, Guangxue Liu, Yueyue Zhang, Lun Song, Gang Cai, Qing Li, Grzegorz Ira, Xinghua Zhang, Xuefeng Chen
Summary: Rtt105 plays a critical role in high-fidelity DNA replication and recombination by regulating RPA, while also suppressing repair through deleterious pathways. Its human homolog, hRIP-alpha, displays similar functions, suggesting conservation of the Rtt105-mediated mechanism.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biology
Enjie Li, Mingyue Xia, Yu Du, Kaili Long, Feng Ji, Feiyan Pan, Lingfeng He, Zhigang Hu, Zhigang Guo
Summary: This study reveals the involvement of METTL3 in the regulation of homologous recombination repair (HR) and chemotherapeutic response in breast cancer cells. It also demonstrates the role of METTL3 in the m6A modification of the EGF/RAD51 axis, which affects HR activity and DNA damage.
Article
Biotechnology & Applied Microbiology
Shenli Yuan, Tao Huang, Ziyou Bao, Shiyu Wang, Xinyue Wu, Jiang Liu, Hongbin Liu, Zi-Jiang Chen
Summary: The histone methylation reader ZCWPW1 is essential for maintaining H3K9ac by antagonizing HDAC proteins' deacetylation activity, promoting chromatin openness at recombination hotspots and enhancing homologous recombination during meiotic double-strand break repair. Ectopic expression of the germ-cell-specific protein ZCWPW1 in human somatic cells enhances double-strand break repair via homologous recombination, providing new insights into the regulation of meiotic homologous recombination by histone modifications and regulatory proteins.
Article
Biochemistry & Molecular Biology
Gaetana Sessa, Belen Gomez-Gonzalez, Sonia Silva, Carmen Perez-Calero, Romane Beaurepere, Sonia Barroso, Sylvain Martineau, Charlotte Martin, Asa Ehlen, Juan S. Martinez, Berangere Lombard, Damarys Loew, Stephan Vagner, Andres Aguilera, Aura Carreira
Summary: BRCA2-deficient cells accumulate DNA-RNA hybrids, and the BRCA2-DDX5 interaction helps in unwinding these structures, enhancing helicase activity and promoting repair of double-strand breaks.
Article
Plant Sciences
Chen Yu, Longhui Hou, Yongchi Huang, Xiaoyu Cui, Shijun Xu, Lili Wang, Shunping Yan
Summary: DNA double-strand breaks (DSBs) are highly hazardous to cells, and homologous recombination (HR) is an accurate repair mechanism for DSBs and gene targeting. However, the understanding of the HR mechanism in plants is limited. Through genetic screening, the Arabidopsis ddrm2 mutant, which is highly conserved in plants, was found to be hypersensitive to DSB-inducing reagents. The plant-specific transcription factor SOG1 activates the expression of DDRM2, which functions downstream of SOG1. DDRM2 interacts with RAD51 and is necessary for RAD51 recruitment to DSB sites. This study reveals a novel HR module and a potential target for improving gene targeting efficiency.
Article
Cell Biology
Yu Sun, Dan Dong, Yuhong Xia, Liying Hao, Wei Wang, Chenghai Zhao
Summary: YTHDF1 plays a tumor-promoting role in breast cancer and is involved in DNA damage repair by modulating E2F8. Inhibition of YTHDF1 can enhance the sensitivity of breast cancer cells to chemotherapy drugs.
CELL DEATH & DISEASE
(2022)
Article
Biochemistry & Molecular Biology
Sijie Liu, Yu Hua, Jingna Wang, Lingyan Li, Junjie Yuan, Bo Zhang, Ziyang Wang, Jianguo Ji, Daochun Kong
Summary: Protection of 30 overhangs in DNA double-strand breaks (DSBs) repair is achieved through the transient formation of RNA-DNA hybrids, with RNA polymerase III (RNAPIII) responsible for synthesizing the RNA strand. CtIP and MRN nuclease activity are required for initiating RNAPIII-mediated RNA synthesis at DSBs. Reduced RNAPIII levels suppress homologous recombination (HR) and lead to genetic loss > 30 bp at DSBs.
Article
Biochemistry & Molecular Biology
Xiaolu Ma, Chen Wang, Bo Zhou, Zina Cheng, Zhiyong Mao, Tie-Shan Tang, Caixia Guo
Summary: This study demonstrated the important role of Pol eta in ETO-induced DSB repair, and identified Kap1 as a novel regulator. Kap1 regulates the function of Pol eta in DSB repair by facilitating Rad18 recruitment and stabilizing the Rad18-Pol eta association.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Jiao Zhao, Shanshan Tian, Qiushi Guo, Kaiwen Bao, Guohui Yu, Xiaodan Wang, Xilin Shen, Jieyou Zhang, Jiaxin Chen, Ying Yang, Ling Liu, Xiangchun Li, Jihui Hao, Na Yang, Zhe Liu, Ding Ai, Jie Yang, Yi Zhu, Zhi Yao, Shuai Ma, Kai Zhang, Lei Shi
Summary: The efficiency of homologous recombination (HR) in DNA double-strand break (DSB) repair is closely related to genome stability and tumor response to chemotherapy. This study reveals that TOPBP1 interacts with the RNA-binding protein HTATSF1 in a cell-cycle and phosphorylation-dependent manner. CK2 phosphorylates HTATSF1, promoting its binding to TOPBP1, which then facilitates S-phase-specific TOPBP1 recruitment to damaged chromatin and subsequent HR, genome integrity, and cancer-cell viability. The localization of HTATSF1-TOPBP1 to DSBs is potentially independent of its role in transcription-coupled RNA-binding and processing, but relies on the recognition of poly(ADP-ribosyl)ated RPA by HTATSF1, which can be inhibited by PARP inhibitors.
Article
Multidisciplinary Sciences
Ethan S. Lavi, Z. Ping Lin, Elena S. Ratner
Summary: This study investigated the effects of non-homologous end-joining (NHEJ) genes on clinical outcomes of ovarian cancer patients, and identified several most important genes for predicting the prognosis of ovarian cancer patients.
Article
Oncology
Zhipeng Du, Fangxiao Zhang, Lei Liu, Hui Shen, Tingting Liu, Jing Jin, Nanxi Yu, Zhijie Wan, Hang Wang, Xuguang Hu, Yuanyuan Chen, Jianming Cai
Summary: This study reveals that the lncRNA ANRIL targets the miR-7-5p/PARP1 axis to regulate DNA damage repair, suggesting that modulating ANRIL expression could be a promising approach to overcome radiation resistance.
Article
Biochemistry & Molecular Biology
Min Kyung Ju, Joo Rak Lee, Yeonsong Choi, Seon Young Park, Hee Jung Sul, Hee Jin Chung, Soyeong An, Semin Lee, Eunyoung Jung, Bohyun Kim, Bo Youn Choi, Bum Jun Kim, Hyeong Su Kim, Hyun Lim, Ho Suk Kang, Jae Seung Soh, Kyungjae Myung, Kab Choong Kim, Ji Woong Cho, Jinwon Seo, Tae Moon Kim, Ja Yil Lee, Yonghwan Kim, Hongtae Kim, Dae Young Zang
Summary: PWWP2B, one of the most frequently mutated genes in gastric adenocarcinoma, plays a role in DNA double-strand break repair by moving to sites of DNA damage through its interaction with UHRF1. It interacts with MRE11 and participates in homologous recombination by promoting DNA end-resection, facilitating DNA repair machinery recruitment and promoting HR-mediated DNA double-strand break repair.
Article
Oncology
Adam D. Brown, Scott Greenman, Alison B. Claybon, Alexander J. R. Bishop
Summary: BRCA1 or BRCA2 inherited mutations are linked to familial breast and ovarian cancer. BRCA2 plays a crucial role in maintaining genome stability and is necessary for homologous recombination DNA repair in normal tissues, long before the development of cancer. This study demonstrates the importance of BRCA2 in normal tissue proliferation through high-fidelity homologous recombination.
Article
Biochemistry & Molecular Biology
Amelie Schellenbauer, Marie-Noelle Guilly, Romain Grall, Romain Le Bars, Vincent Paget, Thierry Kortulewski, Haser Sutcu, Cecile Mathe, Marie Hullo, Denis Biard, Francois Leteurtre, Vilma Barroca, Youenn Corre, Lamya Irbah, Emilie Rass, Benoit Theze, Pascale Bertrand, Jeroen A. A. Demmers, Josee Guirouilh-Barbat, Bernard S. Lopez, Sylvie Chevillard, Jozo Delic
Summary: cNHEJ is a key DNA repair pathway in mammalian cells, regulated by phosphorylation of Ku70 at DNA damage sites, leading to recruitment of RNA Pol II and formation of phospho-53BP1 foci. Phosphorylation is also necessary for the release of Ku70 from the repair complex, and non-phosphorylatable forms may cause chromosomal instability. Cells expressing pKu70 are protected against joining of distal DNA ends, highlighting the essential role of pKu70 in maintaining genome stability.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Medicine, General & Internal
Martine M. Bellanger, Ke Zhou, Sophie A. Lelievre
Summary: The primary prevention of non-communicable diseases, particularly cancer, is challenging and exciting in medicine and primary care. Personalized interventions based on genetic and environmental factors are needed for individuals at risk, with considerations for individual, environmental, and community levels of care.
FRONTIERS IN MEDICINE
(2022)
Review
Oncology
Raya Boyd, Saeed Ahmad, Ratnakar Singh, Zeeshan Fazal, Gail S. Prins, Zeynep Madak Erdogan, Joseph Irudayaraj, Michael J. Spinella
Summary: This review summarizes the molecular research on the potential carcinogenic mechanisms of PFAS, focusing on the three major pathways of metabolism, endocrine disruption, and epigenetic perturbation. It discusses how these interdependent pathways may explain the pro-carcinogenic effects of PFAS and highlights testicular and prostate cancer as models to validate this concept.
Article
Chemistry, Multidisciplinary
Wen Ren, Joseph Irudayaraj
Summary: This study proposes a magnetic control-enhanced lateral flow (MCLF) detection strategy for nucleic acid sequences with high sensitivity. By using magnetic controllers and regulating their movement, the detection limit of the assay is improved. The proposed MCLF technique enables the detection of DNA target sequences as low as 100 aM by naked eyes.
Article
Chemistry, Multidisciplinary
Yi Wen, Wenjie Liu, Benjamin David, Wen Ren, Joseph Irudayaraj
Summary: In this study, a novel multifunctional nanocarrier system was proposed for targeted drug delivery in lung cancer theranostics. This nanocarrier system utilizes oxygenated particles to deliver oxygen to the hypoxic tumor microenvironment, and can also be conjugated with ligands for targeted delivery of the drug doxorubicin. In vitro testing demonstrated that the functionalized nanocarrier system showed increased efficacy against lung cancer cell proliferation, and imaging techniques validated its efficient targeting and tracking capabilities.
Article
Nanoscience & Nanotechnology
Xiaoxue Han, Yoon Jeong, Joseph Irudayaraj
Summary: This study proposes a dual oxygen supply strategy to mitigate hypoxia in the tumor microenvironment. By utilizing enzymes and nanocarriers, oxygen can be released and restore the expression of hypoxia-related genes. The platform is synthesized using safe reagents and has the potential for broad application in treating tumors and other diseases.
ACS APPLIED NANO MATERIALS
(2022)
Article
Engineering, Biomedical
Yoon Jeong, Joseph Irudayaraj
Summary: In order to sequester prokaryotic cells in a biofilm-like niche, it is crucial to create a microenvironment that reflects the heterogeneous nature of biological systems. This study presents an artificial long-term confinement model using natural alginate hydrogels that can support the growth and survival of organisms for over 10 days. The confinement platform allows for the encapsulation of bacterial cells in both the core and shell layers, with tunable thickness and number of shell layers.
ACTA BIOMATERIALIA
(2023)
Article
Biophysics
Yoon Jeong, Wentao Kong, Ting Lu, Joseph Irudayaraj
Summary: In this study, a natural soft hydrogel bioactuator based on alginate core-shell structures was developed to enable 3D microbial colonization at high cell density. Compared to conventional techniques, this system showed a significant increase in cellular biomass, enzymatic activity, and bioluminescence signal, while providing sustained support for bacterial growth within confined space.
BIOSENSORS & BIOELECTRONICS
(2023)
Article
Food Science & Technology
Zhiyang (Stan) Tu, Joseph Irudayaraj, Youngsoo Lee
Summary: This study aimed to enhance the understanding of applying NIR spectroscopy in spray-dried samples by comparing two sample preparation strategies and two spectrometers. The results showed that the sample preparation strategies had little impact on NIR calibration model development. Although the benchtop NIR spectrometer outperformed the portable NIR spectrometer, the portable NIR spectrometer still demonstrated reliable performance for moisture analysis.
Review
Environmental Sciences
Xing Zhang, Jodi A. Flaws, Michael J. Spinella, Joseph Irudayaraj
Summary: Endocrine disrupting chemicals (EDCs) are exogenous substances that can alter the endocrine function of an organism, leading to adverse effects on growth, development, metabolism, and reproductive function. Studies have shown that EDCs can cause proteinuria, affect glomeruli and renal tubules, and even lead to diabetes and renal fibrosis in both animals and humans. This review discusses the renal accumulation of specific EDCs, such as dioxins, per- and polyfluoroalkyl substances (PFAS), bisphenol A (BPA), and phthalates, and explores how exposure to these EDCs can result in renal lesions and diseases, including cancer. The regulation of target genes and activation of related pathways by typical EDCs are also summarized.
Review
Medicine, Research & Experimental
Xiaoxue Han, Leah Suyeon Ju, Joseph Irudayaraj
Summary: Oxygen is crucial in regulating various processes in wound healing. However, hypoxia commonly found in wounds can hinder normal healing. To enhance wound healing, oxygenation strategies such as incorporating oxygen delivery materials are effective. This review summarizes the stages of wound healing, the role of hypoxia, and current strategies for incorporating oxygen into wound dressings. The efficacy, mechanisms, and potential benefits and drawbacks of various oxygenation materials are discussed.
MOLECULAR PHARMACEUTICS
(2023)
Article
Materials Science, Biomaterials
Akshay Krishnakumar, Sachin Kadian, Ulisses Heredia Rivera, Shirisha Chittiboyina, Sophie A. Lelievre, Rahim Rahimi
Summary: Cellular tight junctions regulate the selective passage of solutes across tissues and play a crucial role in establishing barriers between different compartments of the body. In order to better understand the physiology of epithelial tissue when exposed to different substances, efforts have been made to develop clinically relevant organ-on-a-chip models with integrated TEER monitoring systems. However, the high-cost and time-consuming processes required by these platforms limit their scalability in clinical research.
ACS BIOMATERIALS SCIENCE & ENGINEERING
(2023)
Article
Oncology
Julia Holmes, Mohamed Gaber, Monica Z. Jenks, Adam Wilson, Tucker Loy, Cassandra Lepetit, Mara Z. Vitolins, Brittney-Shea Herbert, Katherine L. Cook, Pierre-Alexandre Vidi
Summary: The impact of overweight and obesity on breast cancer risk factors and tissue alterations were investigated in this study. It was found that overweight and obesity were associated with increased proliferation and compromised epithelial polarity in mammary glands. Unfavorable adipokine levels in serum disrupted epithelial polarization, an effect similar to that of leptin. Weight loss and antioxidants were effective in improving tissue markers of risk. This study provides a framework for setting target values for metabolic improvements and evaluating the efficacy of interventions to reduce breast cancer risk.
Article
Environmental Sciences
Faizan Rashid, Veronika Dubinkina, Saeed Ahmad, Sergei Maslov, Joseph Maria Kumar Irudayaraj
Summary: Exposure to PFOS and GenX has different effects on the microbiome of the small intestine and colon, as well as on liver metabolism. High doses of GenX increase the abundance of certain bacteria, while PFOS generally alters the abundance of other bacteria. These treatments are associated with alterations in important microbial metabolic pathways. Additionally, PFOS and GenX exposure can cause metabolic disorders in the liver.
Article
Engineering, Environmental
Yoon Jeong, Khushali Vyas, Joseph Irudayaraj
Summary: This study investigates the toxicity of PFAS on bacteria in a biofilm-like niche provided by hydrogel-based core-shell beads. The findings show that Escherichia coli MG1655 strain confined in hydrogel beads exhibit altered physiological characteristics compared to their susceptible counterpart cultivated under planktonic conditions. The study suggests that soft-hydrogel engineering platforms may protect microorganisms from environmental contaminants.
JOURNAL OF HAZARDOUS MATERIALS
(2023)
Article
Nanoscience & Nanotechnology
Wen Ren, Victoria Messerschmidt, Michael Tsipursky, Joseph Irudayaraj
Summary: In this study, an oxygen nanobubbles-embedded hydrogel (ONB-G) with carbopol was proposed for oxygenation of wounds to accelerate wound healing. ONB-G, prepared by integrating carbopol, hydrogel, and dextran-based oxygen nanobubbles (ONBs), can hold and release oxygen to promote wound healing. Experimental results showed that ONB-G could encapsulate oxygen for up to 34 days and maintain high oxygen levels for up to 4 weeks. HDFa cell-based studies demonstrated the potential of ONB-G in enhancing cell viability, proliferation, and wound closure. Histological evaluation using a pig model also indicated improved healing with ONB-G treatment compared to control groups. Overall, dextran-shell ONBs embedded in a gel exhibit promising potential in accelerating wound healing.
ACS APPLIED NANO MATERIALS
(2023)