Article
Biochemistry & Molecular Biology
Chao Dong, Liwei An, Cheng-han Yu, Michael S. Y. Huen
Summary: The DYRK1B kinase plays a crucial role in maintaining rDNA stability, nucleolar reorganization, and inhibition of rRNA synthesis. Inhibition of DYRK1B results in sustained nucleolar transcription, hypersensitivity to DSBs at rDNA arrays, and requirement for DSB repair and rDNA copy number maintenance. These findings highlight the importance of DYRK1B as a key signaling intermediate in coordinating DSB repair and rDNA transcriptional activities within the nucleolus.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Oncology
Yucheng Liu, Xinyan Wang, Wucheng Zhu, Zhongheng Sui, Xiangqing Wei, Yang Zhang, Jiansong Qi, Yanhong Xing, Wuyang Wang
Summary: This study reveals the mechanism by which TRPML1 inhibits autophagy to regulate apoptosis, involving disrupted mitochondrial turnover, elevated ROS, DNA damage, and p53 activation. These findings have potential clinical implications for treating melanoma and glioblastoma.
Article
Cell Biology
Chao Mei, Ze-En Sun, Li-Ming Tan, Jian-Ping Gong, Xi Li, Zhao-Qian Liu
Summary: Our study demonstrates that eIF3a continuously activates the ATM/ATR signaling pathway by inhibiting the translation of PPP2R5A, leading to chronic phosphorylation and activation of ATM/ATR. This impairs DNA repair and enhances the sensitivity to irinotecan.
CELL PROLIFERATION
(2022)
Review
Genetics & Heredity
Sivakumar Vadivel Gnanasundram, Ondrej Bonczek, Lixiao Wang, Sa Chen, Robin Fahraeus
Summary: Continuous genotoxic stress attacks challenge human cells, leading to DNA damage and potentially cancer development. Cells activate the DNA damage response (DDR) to regulate the cell cycle and repair DNA, with the tumor suppressor p53 playing a key role in this process.
Review
Biochemistry & Molecular Biology
Eleanor Sheekey, Masashi Narita
Summary: The tumour suppressor p53 plays a central role in cellular senescence by regulating both senescence-associated stable proliferative arrest and the secretion of bioactive factors known as the senescence-associated secretory phenotype (SASP). Senescence is associated with various physiological and pathological conditions, including ageing, cancer, and other age-related disorders. Cell functions are determined by the expression of lineage-specific genes, which are also influenced by p53. Additionally, p53 is tightly regulated at the protein level, and its activity is sustained and fine-tuned during senescence and other prolonged pathological conditions.
Article
Biochemistry & Molecular Biology
Jingjie Yi, Huan Li, Bo Chu, Ning Kon, Xiaoping Hu, Jianping Hu, Yan Xiong, H. Umit Kaniskan, Jian Jin, Wei Gu
Summary: The oncoprotein FOXM1 acts as a potential driver for tumor growth in triple-negative breast cancers (TNBC), and USP7 stabilizes FOXM1 through deubiquitination, promoting TNBC cell growth. The USP7 degrader PU7-1 effectively suppresses FOXM1 functions and inhibits TNBC cell growth. These findings reveal the potential therapeutic use of a USP7 degrader for the treatment of TNBC.
CELL DEATH AND DIFFERENTIATION
(2023)
Article
Multidisciplinary Sciences
C. Fritsch, J-F Gout, S. Haroon, A. Towheed, C. Chung, J. LaGosh, E. McGann, X. Zhang, Y. Song, S. Simpson, P. S. Danthi, B. A. Benayoun, D. Wallace, K. Thomas, M. Lynch, M. Vermulst
Summary: Research shows that mutagenic compounds not only cause genetic mutations, but are also a powerful source of transcription errors. These errors occur in both dividing and nondividing cells, and sometimes greatly exceed the number of mutations in the genome. Additionally, DNA repair is crucial in mitigating transcriptional mutagenesis after exposure to mutagens.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biochemistry & Molecular Biology
Linke Tang, Weifeng Yuan, Shitao Li, Xiuyan Ding, Liqian Zhu
Summary: In this study, the interaction between UV-primed global DDR and BoHV-1 productive infection was demonstrated. UV-primed global DDR differentially modulated the transcription of virus genes and stabilization of virus protein. Vice versa, the virus infection may affect UV-primed DDR signaling.
Article
Biochemistry & Molecular Biology
Yanxia Wu, Yanxi Sun, Binchu Xu, Mo Yang, Xingwu Wang, Xiaocheng Zhao
Summary: The lncRNA SCARNA10 interacts with the DNA binding domain (DBD) of the tumor suppressor p53, promoting its acetylation modification and activating p53-mediated transcriptional activity. This involvement of SCARNA10 in various cellular processes such as cell cycle arrest, apoptosis, DNA repair, cell metabolism, and ferroptosis highlights its importance in tumor suppression.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Romain Villot, Audrey Poirier, Inan Bakan, Karine Boulay, Erlinda Fernandez, Romain Devillers, Luciano Gama-Braga, Laura Tribouillard, Andreanne Gagne, Ema Duchesne, Danielle Caron, Jean-Sebastien Berube, Jean-Christophe Berube, Yan Coulombe, Michele Orain, Yves Gelinas, Stephane Gobeil, Yohan Bosse, Jean-Yves Masson, Sabine Elowe, Steve Bilodeau, Venkata Manem, Philippe Joubert, Frederick A. Mallette, Mathieu Laplante
Summary: The study reveals that RAS activation destabilizes the transcription factor ZNF768, leading to cellular senescence by derepression of the p53 pathway; Overexpression of ZNF768 can bypass RAS-induced senescence and promote proliferation; ZNF768 is often overexpressed in tumors, suggesting its role in evading senescence and promoting malignant transformation.
NATURE COMMUNICATIONS
(2021)
Review
Oncology
Jayaraman Krishnaraj, Tatsuki Yamamoto, Rieko Ohki
Summary: Acquired resistance to chemoradiotherapy is a common cause of cancer treatment failure. Cancer cells exploit the tumor suppressor p53 to activate cytoprotective mechanisms such as the DNA damage response, immediate early response gene 5/heat-shock factor 1 pathway, and p21/nuclear factor erythroid 2-related factor 2 pathway. These pathways protect cancer cells from the toxic effects of radiation and drugs, leading to resistance to chemoradiotherapy.
Article
Biochemistry & Molecular Biology
Ling Zhang, Laura Misiara, Govindi J. Samaranayake, Nisha Sharma, Dao M. Nguyen, Yu-Ki Tahara, Eric T. Kool, Priyamvada Rai
Summary: The co-inhibition of OGG1/MTH1 is unlikely to yield significant tumor-suppressive benefit, instead it may exert tumor-protective effects.
Article
Pharmacology & Pharmacy
Yanting Yang, Xiuhong Zhu, Guohua Yu, Jinbo Ma
Summary: This study demonstrates that Pyxinol can mitigate cisplatin-induced renal injury by attenuating DNA damage response and tubular cell apoptosis. Furthermore, Pyxinol can enhance the in vivo anti-tumor efficacy of cisplatin against xenograft tumors in nude mice. The combination of Pyxinol with cisplatin may represent a beneficial adjunct therapy for cisplatin-based chemotherapeutic regimens in the clinic.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Multidisciplinary Sciences
Shaliny Ramachandran, Tiffany S. Ma, Jon Griffin, Natalie Ng, Iosifina P. Foskolou, Ming-Shih Hwang, Pedro Victori, Wei-Chen Cheng, Francesca M. Buffa, Katarzyna B. Leszczynska, Sherif F. El-Khamisy, Natalia Gromak, Ester M. Hammond
Summary: Hypoxia induces a unique cellular transcriptional response, including the accumulation of R-loops and the induction of the RNA/DNA helicase SETX. SETX plays a critical role in protecting cells from DNA damage induced during transcription in hypoxia, and its induction mechanism in hypoxia relies on the PERK/ATF4 arm of the unfolded protein response.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Biao Zhang, Yi Li, Jieyou Zhang, Yuejiao Wang, Can Liang, Ting Lu, Chunyong Zhang, Ling Liu, Yan Qin, Jiahuan He, Xiangnan Zhao, Jia Yu, Jihui Hao, Jie Yang, Mulin Jun Li, Zhi Yao, Shuai Ma, Hui Cheng, Tao Cheng, Lei Shi
Summary: Unscheduled R-loops can cause replication stress and DNA damage. The nuclear form of RNA-editing enzyme ADAR1 promotes ATR activation and resolves genome-wide R-loops. ADAR1 interacts with TOPBP1 and enhances its association with RAD9 to address replication fork issues. When replication is inhibited, DNA-RNA hybrid competes with TOPBP1 for ADAR1 binding, leading ADAR1 to translocate from damaged forks to R-loop regions. There, ADAR1 recruits RNA helicases DHX9 and DDX21 to unwind R-loops and enhance ATR activity.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Biochemical Research Methods
Vladimir Perovic, Neven Sumonja, Branislava Gemovic, Eneda Toska, Stefan G. Roberts, Nevena Veljkovic
Article
Cell Biology
Jayasha Shandilya, Kathryn F. Medler, Stefan G. E. Roberts
Article
Biochemistry & Molecular Biology
Juan Wang, Shasha Zhao, Wei He, Yun Wei, Yang Zhang, Henry Pegg, Paul Shore, Stefan G. E. Roberts, Wensheng Deng
JOURNAL OF BIOLOGICAL CHEMISTRY
(2017)
Article
Cell Biology
Lindsey A. Marsh, Samantha Carrera, Jayasha Shandilya, Kate J. Heesom, Andrew D. Davidson, Kathryn F. Medler, Stefan Ge Roberts
CELL DEATH & DISEASE
(2017)
Article
Multidisciplinary Sciences
Vladimir Perovic, Neven Sumonja, Lindsey A. Marsh, Sandro Radovanovic, Milan Vukicevic, Stefan G. E. Roberts, Nevena Veljkovic
SCIENTIFIC REPORTS
(2018)
Article
Physiology
Tapan K. Nayak, Ridhima Vij, Iva Bruhova, Jayasha Shandilya, Anthony Auerbach
JOURNAL OF GENERAL PHYSIOLOGY
(2019)
Article
Endocrinology & Metabolism
Zachary C. Ahart, Laura E. Martin, Bailey R. Kemp, Debarghya Dutta Banik, Stefan G. E. Roberts, Ann-Marie Torregrossa, Kathryn F. Medler
Article
Biochemistry & Molecular Biology
Tareg Belali, Chigeru Wodi, Bethany Clark, Man-Kim Cheung, Tim J. Craig, Gabrielle Wheway, Nicole Wagner, Kay-Dietrich Wagner, Stefan Roberts, Sean Porazinski, Michael Ladomery
BIOCHIMICA ET BIOPHYSICA ACTA-GENE REGULATORY MECHANISMS
(2020)
Article
Multidisciplinary Sciences
Amy E. Loats, Samantha Carrera, Anna F. Fleming, Abigail R. E. Roberts, Alice Sherrard, Eneda Toska, Alexander J. Moorhouse, Kathryn F. Medler, Stefan G. E. Roberts
Summary: The study reveals that the lipidated protein BASP1 recruits cholesterol to the promoter region of target genes in the cell nucleus through a conserved interaction motif, and that BASP1's interaction with cholesterol is required for chromatin remodeling and the direction of transcription programs controlling cell differentiation.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Letter
Hematology
Megan Wagstaff, Olga Tsaponina, Gilian Caalim, Hayley Greenfield, Leanne Milton-Harris, Erika J. Mancini, Allison Blair, Kate J. Heesom, Alex Tonks, Richard L. Darley, Stefan G. Roberts, Rhys G. Morgan
Article
Multidisciplinary Sciences
Alexander J. Moorhouse, Amy E. Loats, Kathryn F. Medler, Stefan G. E. Roberts
Summary: The transcriptional corepressor BASP1 requires N-terminal myristoylation for its activity and functions through interactions with nuclear lipids. Removal of active histone modifications H3K9ac and H3K4me3 by BASP1 requires N-terminal myristoylation, while placement of the repressive histone modification H3K27me3 does not require lipidation. BASP1 regulates activity of multiple transcription factors and induces extensive changes in chromatin accessibility, with about 50% of BASP1 target genes showing lipidation-dependent chromatin compaction and transcriptional repression.
Article
Oncology
Anuj Anuj, Nina Reuven, Stefan G. E. Roberts, Ari Elson
Summary: The cytokine RANKL is involved in the differentiation of monocytes/macrophages into bone-resorbing osteoclasts, and it down-regulates the expression of BASP1 which is a negative regulator of osteoclastogenesis. Knocking down or eliminating BASP1 enhances RANKL-induced osteoclastogenesis, promoting cell-cell fusion and increasing mineral degrading abilities of osteoclasts.
EXPERIMENTAL CELL RESEARCH
(2023)
Article
Biology
Yankun Gao, Debarghya Dutta Banik, Mutia M. Muna, Stefan G. E. Roberts, Kathryn F. Medler
LIFE SCIENCE ALLIANCE
(2019)
Meeting Abstract
Behavioral Sciences
Kathryn F. Medler, Yankun Gao, Jayasha Shandilya, Stefan G. E. Roberts