Article
Multidisciplinary Sciences
Soon-Keat Ooi, Shigeo Sato, Chieri Tomomori-Sato, Ying Zhang, Zhihui Wen, Charles A. S. Banks, Michael P. Washburn, Jay R. Unruh, Laurence Florens, Ronald C. Conaway, Joan W. Conaway
Summary: PARP1 has multiple functions in ALC1-dependent nucleosome remodeling beyond simply synthesizing PAR chains, as shown by investigation of separation-of-function mutants that activate ALC1 ATPase but do not support nucleosome remodeling by ALC1.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biology
Luka Bacic, Guillaume Gaullier, Anton Sabantsev, Laura C. Lehmann, Klaus Brackmann, Despoina Dimakou, Mario Halic, Graeme Hewitt, Simon J. Boulton, Sebastian Deindl
Summary: Here, we reconstituted an ALC1 and PARylated nucleosome complex modified in vitro, enabling cryo-EM structure determination to visualize several intermediate states of ALC1. Functional biochemical assays with PARylated nucleosomes highlighted the importance of nucleosomal epitopes for productive remodeling, and suggested that ALC1 prefers sliding nucleosomes away from DNA breaks.
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
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
Biochemistry & Molecular Biology
Elena Y. Kotova, Fu-Kai Hsieh, Han-Wen Chang, Natalia Maluchenko, Marie-France Langelier, John M. Pascal, Donal S. Luse, Alexey Feofanov, Vasily M. Studitsky
Summary: This study investigated the role of human PARP1 in transcription through nucleosomes and found that PARP1 facilitates transcription and displacement of core histones during transcription through its NAD+-dependent catalytic activity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
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
Multidisciplinary Sciences
Evgeniia Prokhorova, Florian Zobel, Rebecca Smith, Siham Zentout, Ian Gibbs-Seymour, Kira Schutzenhofer, Alessandra Peters, Josephine Groslambert, Valentina Zorzini, Thomas Agnew, John Brognard, Michael L. Nielsen, Dragana Ahel, Sebastien Huet, Marcin J. Suskiewicz, Ivan Ahel
Summary: Recent findings suggest that serine ADP-ribosylation plays a vital role in cellular responses to PARP1/PARP2 inhibitors. The efficient modification of three serine residues within PARP1 by HPF1 counters PARP1 trapping and contributes to inhibitor tolerance, implicating these residues as potential biomarkers for PARP inhibitor therapy.
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)
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
Johannes Rudolph, Karolin Luger
Summary: The auxiliary factor HPF1 redirects the enzymatic activity of PARP1, altering the PAR modification of proteins and affecting DNA repair in cells.
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Lotte van Beek, Eilis McClay, Saleha Patel, Marianne Schimpl, Laura Spagnolo, Taiana Maia de Oliveira
Summary: PARP 1-3 are multi-domain enzymes known for catalyzing covalent modification of proteins, DNA, and themselves, with important functions in DNA damage response and nucleosome remodelling. Activation of PARP occurs through DNA binding, and modulation of their activity with PARP inhibitors has shown success in cancer therapies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(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
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
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
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
Juston C. Weems, Brian D. Slaughter, Jay R. Unruh, Shawn M. Hall, Merry B. McLaird, Joshua M. Gilmore, Michael P. Washburn, Laurence Florens, Takashi Yasukawa, Teijiro Aso, Joan W. Conaway, Ronald C. Conaway
JOURNAL OF BIOLOGICAL CHEMISTRY
(2015)
Editorial Material
Cell Biology
Ronald C. Conaway, Joan W. Conaway
NATURE REVIEWS MOLECULAR CELL BIOLOGY
(2015)
Correction
Multidisciplinary Sciences
Trent Fowler, Payel Ghatak, David H. Price, Ronald Conaway, Joan Conaway, Cheng-Ming Chiang, James E. Bradner, Ali Shilatifard, Ananda L. Roy
Article
Multidisciplinary Sciences
Yasushi Masuda, Hidehisa Takahashi, Shigeo Sato, Chieri Tomomori-Sato, Anita Saraf, Michael P. Washburn, Laurence Florens, Ronald C. Conaway, Joan W. Conaway, Shigetsugu Hatakeyama
NATURE COMMUNICATIONS
(2015)
Article
Biochemistry & Molecular Biology
Juston C. Weems, Brian D. Slaughter, Jay R. Unruh, Stefan Boeing, Shawn M. Hall, Merry B. McLaird, Takashi Yasukawa, Teijiro Aso, Jesper Q. Svejstrup, Joan W. Conaway, Ronald C. Conaway
JOURNAL OF BIOLOGICAL CHEMISTRY
(2017)
Article
Biochemistry & Molecular Biology
Kuang-Lei Tsai, Chieri Tomomori-Sato, Shigeo Sato, Ronald C. Conaway, Joan W. Conaway, Francisco J. Asturias
Correction
Biochemistry & Molecular Biology
Kuang-Lei Tsai, Chieri Tomomori-Sato, Shigeo Sato, Ronald C. Conaway, Joan W. Conaway, Francisco J. Asturias
Article
Biochemistry & Molecular Biology
Mihaela E. Sardiu, Joshua M. Gilmore, Brad D. Groppe, Damir Herman, Sreenivasa R. Ramisetty, Yong Cai, Jingji Jin, Ronald C. Conaway, Joan W. Conaway, Laurence Florens, Michael P. Washburn
Article
Multidisciplinary Sciences
Trent Fowler, Payel Ghatak, David H. Price, Ronald Conaway, Joan Conaway, Cheng-Ming Chiang, James E. Bradner, Ali Shilatifard, Ananda L. Roy
Article
Multidisciplinary Sciences
Lanfeng Wang, Oliver Limbo, Jia Fei, Lu Chen, Bong Kim, Jie Luo, Jenny Chong, Ronald C. Conaway, Joan W. Conaway, Jeff A. Ranish, James T. Kadonaga, Paul Russell, Dong Wang
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2014)
Article
Multidisciplinary Sciences
Melvin Noe Gonzalez, Shigeo Sato, Chieri Tomomori-Sato, Joan W. Conaway, Ronald C. Conaway
NATURE COMMUNICATIONS
(2018)
Article
Biochemistry & Molecular Biology
Ronald C. Conaway, Joan W. Conaway
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2019)
Article
Biochemistry & Molecular Biology
Juston C. Weems, Brian D. Slaughter, Jay R. Unruh, Kyle J. Weaver, Brandon D. Miller, Kym M. Delventhal, Joan W. Conaway, Ronald C. Conaway
Summary: The CSB-Elongin ubiquitin ligase pathway not only plays a role in the response to DNA damage, but also has a significant impact on the activation of RNAPII-mediated transcription in various signaling pathways, such as endoplasmic reticulum stress, amino acid starvation, retinoic acid, glucocorticoids, and doxycycline. The pathway is involved in the rapid recruitment of CSB and the Elongin ubiquitin ligase to target genes during transcription, suggesting a direct role in gene regulation. Cells lacking the Elongin subunit Elongin A exhibit delays in RNAPII accumulation and dismissal from target genes following hormone treatments, indicating the importance of this pathway in transcription regulation.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Multidisciplinary Sciences
Yanfeng He, Shigeo Sato, Chieri Tomomori-Sato, Shiyuan Chen, Zach H. Goode, Joan W. Conaway, Ronald C. Conaway
Summary: The bZIP transcription factor ATF6 alpha is a master regulator of ER stress response genes, with the multifunctional RNA polymerase II transcription factor Elongin identified as a cofactor for ATF6 alpha-dependent transcription activation. Studies show that Elongin facilitates ATF6 alpha-dependent loading of Mediator at the promoters and enhancers of ER stress response genes, and depletion of Elongin leads to impaired transcription and recruitment of Mediator and its CDK8 kinase subunit during the ER stress response. Overall, these findings reveal a crucial role for Elongin as a loading factor for Mediator in the context of ER stress response.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Genetics & Heredity
Jaya Krishnan, Chris W. Seidel, Ning Zhang, Narendra Pratap Singh, Jake VanCampen, Robert Peuss, Shaolei Xiong, Alexander Kenzior, Hua Li, Joan W. Conaway, Nicolas Rohner
Summary: Cis-regulatory changes have been found to contribute to the metabolic adaptation in different morphotypes of Astyanax mexicanus, with genetically diverged and differentially regulated elements identified between surface and cave populations. This study sheds light on the molecular mechanisms underlying metabolic adaptations to nutrient-deprived cave environments.