Article
Biochemistry & Molecular Biology
Waghela Deeksha, Suman Abhishek, Eerappa Rajakumara
Summary: Poly(ADP-ribosyl)ation is mainly catalyzed by Poly(ADP-ribose) polymerase 1 (PARP1) in response to DNA damage, mediating the DNA repair process to maintain genomic integrity. Single-strand (SSB) and double-strand (DSB) DNA breaks are bona fide stimulators of PARP1 activity. However, PAR-mediated PARP1 regulation remains unexplored.
Article
Biochemistry & Molecular Biology
Natalya V. Maluchenko, Dmitry K. Nilov, Sergey V. Pushkarev, Elena Y. Kotova, Nadezhda S. Gerasimova, Mikhail P. Kirpichnikov, Marie-France Langelier, John M. Pascal, Md. Sohail Akhtar, Alexey V. Feofanov, Vasily M. Studitsky
Summary: The mechanisms of PARP1-nucleosome interaction are still unknown, with potential for PARP1-induced nucleosome reorganization to form an alternative state likely involved in gene regulation and DNA repair.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Fa-Hui Sun, Peng Zhao, Nan Zhang, Lu-Lu Kong, Catherine C. L. Wong, Cai-Hong Yun
Summary: Poly(ADP-ribose) polymerase 1 (PARP1) ADP-ribosylates itself and other DNA repair factors to initiate the repair process upon DNA damage, with our high-resolution crystal structures of HPF1 and HPF1/PARP1 complex providing insights into PARP1 regulation.
NATURE COMMUNICATIONS
(2021)
Article
Cell Biology
Arnold Tan, Awais Z. Younis, Alexander Evans, Jade V. Creighton, Clare Coveny, David J. Boocock, Craig Sale, Gareth G. Lavery, Amanda S. Coutts, Craig L. Doig
Summary: The PARP1 enzyme generates and applies ADP-Ribose, a post-translational modification. PARP1 plays important roles in genome maintenance, cellular identity, and energy homeostasis. In skeletal muscle cells, PARP1-mediated PARylation regulates the myogenic program and the muscle response to steroid hormones. PARylation is sensitive to glucose concentrations and glucocorticoids, which are crucial for muscle development and metabolism. PARP1 also influences the transcriptional activation of specific genes critical to skeletal muscle pathology, providing potential targets for selective glucocorticoid modulation.
CELL DEATH DISCOVERY
(2023)
Article
Cell Biology
Natalya Maluchenko, Darya Koshkina, Anna Korovina, Vasily Studitsky, Alexey Feofanov
Summary: The cytotoxicity of poly(ADP-ribose-)polymerase-1 (PARP1) inhibitors (PARPi) in antitumor therapy is correlated with their trapping efficiency in cell chromatin. The interactions of PARP1-nucleosome complexes with PARPi were studied, and it was found that the efficiency of PARP1 trapping on nucleosomes is affected by the chromatin structure.
Article
Multidisciplinary Sciences
Johannes Rudolph, Genevieve Roberts, Karolin Luger
Summary: PARP1 and PARP2 are key enzymes in the DNA damage response. HPF1 plays an essential role in modulating the PARylation of histones by forming a complex with both PARP1 and PARP2. Results show how HPF1 can affect the binding affinity of certain inhibitors to PARP1.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Leonie Frigon, John M. Pascal
Summary: PARP4 is an ADP-ribosyltransferase that resides within the vault ribonucleoprotein organelle. This study provides insights into PARP4 structure and regulation, revealing that the catalytic domain of PARP4 has an open active site for NAD+ interaction. Crystal structures of the minimal ADP-ribosyltransferase fold of PARP4 illustrate active site alterations that restrict PARP4 to mono(ADP-ribose) modifications. PARP4 interacts with vault RNA primarily through the BRCT region, but this interaction does not stimulate mono(ADP-ribosylation) activity. The BRCT and WGR domains of PARP4 regulate its catalytic output.
NUCLEIC ACIDS RESEARCH
(2023)
Review
Biochemistry & Molecular Biology
Dan Huang, W. Lee Kraus
Summary: ADP-ribosylation is a post-translational modification of proteins catalyzed by ADP-ribosyl transferase enzymes. PARP1, as a member of the nuclear PARPs family, plays important roles in DNA repair, chromatin regulation, and gene expression. Recent studies have expanded our understanding of the diverse functions of ADP-ribosylation in various biological processes.
Article
Food Science & Technology
Souren Paul, Rekha Jakhar, Monika Bhardwaj, Anil Kumar Chauhan, Sun Chul Kang
Summary: The study found that Fumonisin B1 exerts its toxicity on neuroblastoma cells through the parthanatos pathway, causing DNA damage and cell death, while also inducing endoplasmic reticulum stress and chromatin decondensation.
FOOD AND CHEMICAL TOXICOLOGY
(2021)
Article
Biology
Johannes Rudolph, Genevieve Roberts, Uma M. Muthurajan, Karolin Luger
Summary: HPF1 redirects PARylation by PARP1 towards histones, leading to shorter PAR chains and production of free ADP-ribose. This switch from polymerase to hydrolase has important implications for DNA damage response mediated by PARP1 and raises questions about intracellular ADPR and depletion of NAD(+).
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
Microbiology
Woo-Chang Chung, Seungrae Lee, Yejin Kim, Jong Bok Seo, Moon Jung Song
Summary: KSHV utilizes PF-8 and cellular E3 ligase CHFR to degrade PARP1 and overcome its inhibitory effect on viral lytic replication, thus enhancing KSHV replication process.
Review
Immunology
Carlos Wagner S. Wanderley, Tatiana Strava Correa, Mariana Scaranti, Fernando Queiroz Cunha, Romualdo Barroso-Sousa
Summary: The use of immune checkpoint inhibitors (ICIs) in cancer treatment has revolutionized the field, but prolonged use of ICIs has resulted in a specific response to certain types of cancer. To overcome resistance and improve outcomes, researchers have explored novel strategies involving the combination of ICIs with other therapies. One promising class of agents is poly ADP-ribose polymerase inhibitors (PARPi), which have the potential to enhance the antitumor immune response through various mechanisms.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Multidisciplinary Sciences
Fen Yang, Jianji Chen, Bin Liu, Guozhen Gao, Manu Sebastian, Collene Jeter, Jianjun Shen, Maria D. Person, Mark T. Bedford
Summary: SPINDOC interacts with histone code effector protein SPIN1 and forms two distinct protein complexes, one with SPIN1 and the other with PARP1. It plays a role in regulating PARP1-mediated PARylation and the DNA damage response. Knockout of SPINDOC leads to reduced PARylation levels, smaller body size in mice, and hypersensitivity to IR-induced DNA damage.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Johannes Rudolph, Uma M. Muthurajan, Megan Palacio, Jyothi Mahadevan, Genevieve Roberts, Annette H. Erbse, Pamela N. Dyer, Karolin Luger
Summary: PARP1 is a key player in DNA damage response and a target for cancer treatment. The BRCT domain binds to DNA without activating the catalytic domain. The DNA-binding properties of the BRCT domain contribute to the monkey-bar mechanism for DNA transfer of PARP1.
Article
Biochemistry & Molecular Biology
Hossein Aleyasin, Saravanan S. Karuppagounder, Amit Kumar, Sama Sleiman, Manuela Basso, Thong Ma, Ambreena Siddiq, Shankar J. Chinta, Camille Brochier, Brett Langley, Renee Haskew-Layton, Susan L. Bane, Gregory J. Riggins, Irina Gazaryan, Anatoly A. Starkov, Julie K. Andersen, Rajiv R. Ratan
ANTIOXIDANTS & REDOX SIGNALING
(2015)
Article
Chemistry, Medicinal
Mariana C. F. Segretti, Gian Paolo Vallerini, Camille Brochier, Brett Langley, Liqing Wang, Wayne W. Hancock, Alan P. Kozikowski
ACS MEDICINAL CHEMISTRY LETTERS
(2015)
Review
Neurosciences
Victor S. Wong, Brett Langley
NEUROSCIENCE LETTERS
(2016)
Editorial Material
Neurosciences
John W. Cave, Brett Langley, Rajiv R. Ratan
NEUROSCIENCE LETTERS
(2016)
Article
Neurosciences
Sama F. Sleiman, Brett C. Langley, Manuela Basso, Jill Berlin, Li Xia, Jimmy B. Payappilly, Madan K. Kharel, Hengchang Guo, J. Lawrence Marsh, Leslie Michels Thompson, Lata Mahishi, Preeti Ahuja, W. Robb MacLellan, Daniel H. Geschwind, Giovanni Coppola, Juergen Rohr, Rajiv R. Ratan
JOURNAL OF NEUROSCIENCE
(2011)
Article
Neurosciences
Camille Brochier, Gretel Dennis, Mark A. Rivieccio, Kathryn McLaughlin, Giovanni Coppola, Rajiv R. Ratan, Brett Langley
JOURNAL OF NEUROSCIENCE
(2013)
Article
Chemistry, Multidisciplinary
Kyle V. Butler, Jay Kalin, Camille Brochier, Guilio Vistoli, Brett Langley, Alan P. Kozikowski
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2010)
Article
Neurosciences
Thong C. Ma, Brett Langley, Brian Ko, Na Wei, Irina G. Gazaryan, Neela Zareen, Darrell J. Yamashiro, Dianna E. Willis, Rajiv R. Ratan
NEUROBIOLOGY OF DISEASE
(2013)
Review
Clinical Neurology
Camille Brochier, Brett Langley
Review
Clinical Neurology
Brett Langley, Anthony Sauve
Article
Cell Biology
Ashley L. Kalinski, Amar N. Kar, John Craver, Andrew P. Tosolini, James N. Sleigh, Seung Joon Lee, Alicia Hawthorne, Paul Brito-Vargas, Sharmina Miller-Randolph, Ryan Passino, Liang Shi, Victor S. C. Wong, Cristina Picci, Deanna S. Smith, Dianna E. Willis, Leif A. Havton, Giampietro Schiavo, Roman J. Giger, Brett Langley, Jeffery L. Twiss
JOURNAL OF CELL BIOLOGY
(2019)
Article
Neurosciences
Cristina Picci, Victor S. C. Wong, Christopher J. Costa, Marion C. McKinnon, David C. Goldberg, Michelle Swift, Nazia M. Alam, Glen T. Prusky, Sida Shen, Alan P. Kozikowski, Dianna E. Willis, Brett Langley
EXPERIMENTAL NEUROLOGY
(2020)
Article
Chemistry, Medicinal
Sida Shen, Cristina Picci, Kseniya Ustinova, Veronick Benoy, Zsofia Kutil, Guiping Zhang, Mauricio T. Tavares, Jiri Pavlicek, Chad A. Zimprich, Matthew B. Robers, Ludo Van den Bosch, Cyril Barinka, Brett Langley, Alan P. Kozikowski
Summary: The study introduces a new HDAC6 inhibitor, SW-101, which exhibits excellent potency, selectivity, metabolic stability, and druglike properties compared to SW-100. Treatment with SW-101 is shown to improve neuropathic symptoms in a CMT2A mouse model, suggesting its potential as a disease-modifying HDAC6 inhibitor.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Neurosciences
Victor S. C. Wong, Cristina Picci, Michelle Swift, Max Levinson, Dianna Willis, Brett Langley