Article
Biology
Ilirjana Bajrami, Callum Walker, Dragomir B. Krastev, Daniel Weekes, Feifei Song, Andrew J. Wicks, John Alexander, Syed Haider, Rachel Brough, Stephen J. Pettitt, Andrew N. J. Tutt, Christopher J. Lord
Summary: The study investigated the synthetic lethality between BRCA gene defects and inhibition of two sirtuin genes, SIRT1 or SIRT6, which was associated with replication stress and increased PARylation. The authors demonstrated that this synthetic lethality could be reversed by genetic ablation of PARP1 or HPF1.
COMMUNICATIONS BIOLOGY
(2021)
Editorial Material
Biochemistry & Molecular Biology
Michael S. Cohen
Summary: ADP-ribosylation is a crucial post-translational modification, involving MAR and PAR. Researchers have identified distinct MAR and PAR readers using a chemical biology approach.
Article
Biochemistry & Molecular Biology
Jessica Buck, Patrick J. C. Dyer, Hilary Hii, Brooke Carline, Mani Kuchibhotla, Jacob Byrne, Meegan Howlett, Jacqueline Whitehouse, Martin A. Ebert, Kerrie L. McDonald, Nicholas G. Gottardo, Raelene Endersby
Summary: The study showed that PARP inhibitor veliparib enhanced the radiation-induced cytotoxicity of medulloblastoma cells, suggesting that it could be a potential radiosensitizing agent for the treatment of medulloblastoma.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2021)
Article
Cell Biology
Joydeep Mukherjee, Ajay Pandita, Chatla Kamalakar, Tor-Christian Johannessen, Shigeo Ohba, Yongjian Tang, Cecilia L. Dalle-Ore, Rolf Bjerkvig, Russell O. Pieper
Summary: Approximately 10% of tumors, including lower-grade astrocytomas, rely on the ALT mechanism to resolve telomeric shortening. Cells dependent on ALT mechanism are hypersensitive to a subset of PARPi due to PARP1-induced telomere fusion. This study provides a mechanistic insight into how PARP1 recruitment to telomeres in ALT-dependent cells blocks chromosomal fusion, highlighting chromosome fusion as a potential biomarker for PARPi treatment in ALT-dependent tumors.
SCIENCE TRANSLATIONAL MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Masato Mashimo, Akane Morozumi, Akari Nobeyama, Misato Kanzaki, Shigeru Negi, Jiro Kato, Joel Moss, Atsuo Nomura, Takeshi Fujii
Summary: Parthanatos is a programmed cell death process mediated by PARP1, which inhibits endocytosis by binding to Rab5, leading to cell starvation and death.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Engineering, Environmental
Ming-hao Liu, Feng-zheng Li, Wen-jing Liu, Juan Hu, Meng Liu, Chun -Yang Zhang
Summary: A ultrasensitive chemiluminescent biosensor was developed for rapid detection of PARP-1 in human breast tissues. The biosensor combines PARP-1-directed hyperbranched poly(ADP-ribose) formation with alkaline phosphatase-mediated chemiluminescence system. It offers high sensitivity, accuracy, and potential applications in cancer diagnosis and biomedical research.
CHEMICAL ENGINEERING JOURNAL
(2023)
Article
Biochemistry & Molecular Biology
Julia M. Reber, Aswin Mangerich
Summary: Poly(ADP-ribosyl)ation, or PARylation, is a multifaceted post-translational modification with important roles in cellular processes and biomolecular condensate dynamics. Understanding the structural diversity of PAR and its interaction with other post-translational modifications, natural PARP variants, and accessory factors is crucial for the development of new therapeutic approaches. Targeting the enzymatic functions of PARPs, rather than complete inhibition, holds potential for innovative treatments in the future.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Emilia Komulainen, Jack Badman, Stephanie Rey, Stuart Rulten, Limei Ju, Kate Fennell, Ilona Kalasova, Kristyna Ilievova, Peter J. McKinnon, Hana Hanzlikova, Kevin Staras, Keith W. Caldecott
Summary: The study demonstrates that high activity of DNA strand break sensor protein Parp1 in mice with Xrcc1 deletion can result in lethal seizures, which can be prevented and lifespan extended by inhibiting or deleting Parp1. This highlights PARP inhibition as a potential therapeutic approach for hereditary neurological diseases.
Article
Biochemistry & Molecular Biology
Evgeniia Prokhorova, Thomas Agnew, Anne R. Wondisford, Michael Tellier, Nicole Kaminski, Danique Beijer, James Holder, Josephine Groslambert, Marcin J. Suskiewicz, Kang Zhu, Julia M. Reber, Sarah C. Krassnig, Luca Palazzo, Shona Murphy, Michael L. Nielsen, Aswin Mangerich, Dragana Ahel, Jonathan Baets, Roderick J. O'Sullivan, Ivan Ahel
Summary: ARH3 and PARG play different roles in vivo, with ARH3 showing tolerance to MARylation and PARG demonstrating toxicity towards PARylation. There is a synthetic lethal interaction between the two enzymes, and loss of ARH3 can lead to resistance to PARP inhibitors.
Article
Biochemistry & Molecular Biology
Chuanchao Zhang, Bo Zhou, Feng Gu, Hongmei Liu, Honglin Wu, Fuwen Yao, Hui Zheng, Hui Fu, Wei Chong, Shurui Cai, Min Huang, Xiaolu Ma, Zhifang Guo, Tingting Li, Wenyuan Deng, Meiwen Zheng, Qiao Ji, Yongliang Zhao, Yongjie Ma, Qi-En Wang, Tie-Shan Tang, Caixia Guo
Summary: This study identifies a human long noncoding RNA (lncRNA)-derived micropeptide, PACMP, which functions to maintain CtIP abundance and promote poly(ADP-ribosyl)ation. Targeting PACMP inhibits tumor growth through synthetic lethal interaction between CtIP and PARP inhibitions, and enhances sensitivity to various anticancer drugs and radiation.
Article
Oncology
Yves Pommier, Anish Thomas
Summary: ADCs are effective in delivering cytotoxic agents to tumors, and two ADCs delivering TOP1 poisons have been FDA-approved. A recent study introduced a TOP1-anti B7-H4 ADC that showed synergistic effect with a PARP1-selective inhibitor.
CLINICAL CANCER RESEARCH
(2023)
Article
Biology
Sridevi Challa, Keun W. Ryu, Amy L. Whitaker, Jonathan C. Abshier, Cristel Camacho, W. Lee Kraus
Summary: In this study, PAR Trackers were developed and characterized as highly sensitive tools for detecting ADPR in various experimental and biological systems, providing greater temporal and spatial precision.
Article
Oncology
William P. Tew, Christina Lacchetti, Elise C. Kohn
Summary: ASCO Rapid Recommendations Updates provide revisions to select ASCO guideline recommendations based on new and practice-changing data. The goal is to disseminate updated recommendations in a timely manner to inform health practitioners and the public on the best available cancer care options.
JOURNAL OF CLINICAL ONCOLOGY
(2022)
Article
Materials Science, Biomaterials
Ren-Jiang Kong, Xin-Yu Li, Jia-Qi Huang, Xiang Zhou, Fu-An Deng, Yan-Mei Li, Ling-Shan Liu, Shi-Ying Li, Hong Cheng
Summary: A self-delivery photodynamic sensitizer, CeOla, has been developed to enhance oxidative damage and sensitize tumor cells to photodynamic therapy (PDT) by blocking the DNA repair pathway. CeOla, which has a high drug content and favorable water stability, inhibits the activation of PARP, promotes the upregulation of gamma-H2AX, and reduces the expression of Rad51. The self-delivery CeOla greatly promotes tumor cell apoptosis and shows high antitumor performance with low side effects, making it a promising platform for the development of self-delivery nanomedicine to overcome oxidative resistance in tumor treatment.
BIOMATERIALS SCIENCE
(2022)
Article
Oncology
Louise Ramos, Sarah Truong, Beibei Zhai, Jay Joshi, Fariba Ghaidi, Michael M. Lizardo, Taras Shyp, Sonia H. Y. Kung, Alireza M. Rezakhanlou, Htoo Zarni Oo, Hans Adomat, Stephane Le Bihan, Colin Collins, Jeffrey Bacha, Dennis Brown, John Langlands, Wang Shen, Nada Lallous, Poul H. Sorensen, Mads Daugaard
Summary: This study reports a novel bifunctional PARP inhibitor (kt-3283) that has dual activity towards PARP1/2 and HDAC enzymes in Ewing sarcoma cells. Compared to commonly used PARP and HDAC inhibitors, kt-3283 exhibits enhanced cytotoxicity and inhibition effects.
CLINICAL CANCER RESEARCH
(2023)