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
Julia Koritzer, Christian Blenn, Alexander Buerkle, Sascha Beneke
Summary: Conflicting data exist regarding the localization of poly(ADP-ribose) polymerase-1 in mitochondria. Research indicates that while the enzyme itself is not present in mitochondria, a shorter variant of its product can be found associated with specific mitochondrial proteins. This suggests a new mode of nuclear-mitochondrial signaling dependent on poly(ADP-ribose) polymerase-1.
JOURNAL OF CELLULAR BIOCHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Indranil Chatterjee, Deblina Roy, Gautam Panda
Summary: This article reports a scalable and environmentally friendly total synthesis method for a PARP inhibitor. Compared to existing synthesis methods, this method is operationally simple, highly atom economical, and environmentally friendly. The method also includes a key step of phosphonate-free synthesis, which is more convenient compared to previous synthesis methods.
Article
Chemistry, Multidisciplinary
Qiang Liu, Gunnar Knobloch, Jim Voorneveld, Nico J. Meeuwenoord, Herman S. Overkleeft, Gijsbert A. van Der Marel, Andreas G. Ladurner, Dmitri Filippov
Summary: The translation discusses the significance of ADP-ribosylation and the chemical synthesis of linear ADP-ribose oligomers, as well as their affinity for ALC1. The study reveals the length-dependent binding manner of ADPr oligomers to ALC1, illustrating how the activity of this molecular machine is controlled by PAR.
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
Emad Matanes, Vanessa M. Lopez-Ozuna, David Octeau, Tahira Baloch, Florentin Racovitan, Amandeep Kaur Dhillon, Roy Kessous, Oded Raban, Liron Kogan, Shannon Salvador, Susie Lau, Walter H. Gotlieb, Amber Yasmeen
Summary: The study showed that PARG inhibition can complement PARP inhibition in the treatment of ovarian cancer, especially in the presence of homologous recombination defects. PARG inhibitor alone or in combination with PARPi or Cisplatin can reduce cell migration and induce cell death.
FRONTIERS IN ONCOLOGY
(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
Plant Sciences
Jun Hyeok Kim, Laura J. Bell, Xiao Wang, Rinuckshi Wimalasekera, Hugo P. Bastos, Krystyna A. Kelly, Matthew A. Hannah, Alex A. R. Webb
Summary: Our study found that PARPs and sirtuins do not regulate the circadian oscillator in Arabidopsis, but sirtuin 1 is associated with daytime regulation of gene expression.
PLANT CELL AND ENVIRONMENT
(2021)
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
Biochemistry & Molecular Biology
Rebecca Smith, Siham Zentout, Magdalena Rother, Nicolas Bigot, Catherine Chapuis, Alexandra Mihut, Florian Franz Zobel, Ivan Ahel, Haico van Attikum, Gyula Timinszky, Sebastien Huet
Summary: The study reveals that HPF1 is involved in early stages of DNA repair by regulating ADP-ribosylation signaling and damaged chromatin conformation.
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2023)
Article
Chemistry, Physical
Yi-Chih Chiu, Mei-Chun Tseng, Chun-Hua Hsu
Summary: OAADPR, a signaling molecule, is involved in important cellular functions in yeast. Poa1p is an atypical 3''-O-acetyl-ADP-ribose deacetylase that plays a critical role in cellular nucleotide metabolism.
Article
Biochemistry & Molecular Biology
Anna Rita Bianchi, Alessandra La Pietra, Valeria Guerretti, Anna De Maio, Teresa Capriello, Ida Ferrandino
Summary: By studying the brains of adult zebrafish exposed to aluminum, we found hyperactivation of poly(ADPribosyl)ation and changes in the synthesis and degradation of poly(ADP-ribose). The highest activity levels of poly(ADP-ribose) synthesis and degradation were observed after 10 and 15 days of exposure. We hypothesize that the activation of poly(ADP-ribose) polymerase (PARP) is related to aluminum-induced DNA damage, while the activation of poly(ADPR) glycohydrolase (PARG) is necessary to avoid the accumulation of poly(ADP-ribose).
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Multidisciplinary Sciences
Mohsen Badiee, Adam L. Kenet, Laura R. Ganser, Tapas Paul, Sua Myong, Anthony K. L. Leung
Summary: Poly(ADP-ribose) (PAR) is a homopolymer that regulates cellular processes as a posttranslational modification and serves as a scaffold for protein binding in macromolecular complexes. This study demonstrates that PAR has greater stiffness and undergoes sharper compaction in response to cation binding compared to RNA and DNA. The degree of PAR compaction depends on the concentration and valency of cations, and the intrinsically disordered protein FUS can also induce PAR compaction. These findings suggest that a cationic environment may play a role in the recognition specificity of PAR.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Review
Electrochemistry
Ting Sun, Yanying Li, Feng Zhao
Summary: This work summarized the electrochemical strategies for determining PARP-1 activity and screening potential inhibitors.
INTERNATIONAL JOURNAL OF ELECTROCHEMICAL SCIENCE
(2021)
Article
Biochemistry & Molecular Biology
David Hutin, Karoline Alvik Hagen, Peng Shao, Kim Sugamori, Denis M. Grant, Jason Matthews
Summary: PARP7 is an important regulator of the immune system, and is involved in intestinal inflammation. Loss of PARP7 impairs immune response to colon inflammation, possibly due to its role in IFN-I signaling rather than AHR signaling.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Deeksha Munnur, Joanna Somers, George Skalka, Ria Weston, Rebekah Jukes-Jones, Mohammed Bhogadia, Cyril Dominguez, Kelvin Cain, Ivan Ahel, Michal Malewicz
Review
Cell Biology
Johannes Gregor Matthias Rack, Luca Palazzo, Ivan Ahel
GENES & DEVELOPMENT
(2020)
Article
Multidisciplinary Sciences
Marcin J. Suskiewicz, Florian Zobel, Tom E. H. Ogden, Pietro Fontana, Antonio Ariza, Ji-Chun Yang, Kang Zhu, Lily Bracken, William J. Hawthorne, Dragana Ahel, David Neuhaus, Ivan Ahel
Article
Cell Biology
Emeline Lawaree, Gytis Jankevicius, Charles Cooper, Ivan Ahel, Stephan Uphoff, Christoph M. Tang
Article
Multidisciplinary Sciences
Niek van Wietmarschen, Sriram Sridharan, William J. Nathan, Anthony Tubbs, Edmond M. Chan, Elsa Callen, Wei Wu, Frida Belinky, Veenu Tripathi, Nancy Wong, Kyla Foster, Javad Noorbakhsh, Kiran Garimella, Abimael Cruz-Migoni, Joshua A. Sommers, Yongqing Huang, Ashir A. Borah, Jonathan T. Smith, Jeremie Kalfon, Nikolas Kesten, Kasper Fugger, Robert L. Walker, Egor Dolzhenko, Michael A. Eberle, Bruce E. Hayward, Karen Usdin, Catherine H. Freudenreich, Robert M. Brosh, Stephen C. West, Peter J. McHugh, Paul S. Meltzer, Adam J. Bass, Andre Nussenzweig
Article
Biochemistry & Molecular Biology
Graeme Hewitt, Valerie Borel, Sandra Segura-Bayona, Tohru Takaki, Phil Ruis, Roberto Bellelli, Laura C. Lehmann, Lucia Sommerova, Aleksandra Vancevska, Antonia Tomas-Loba, Kang Zhu, Christopher Cooper, Kasper Fugger, Harshil Patel, Robert Goldstone, Deborah Schneider-Luftman, Ellie Herbert, Gordon Stamp, Rachel Brough, Stephen Pettitt, Christopher J. Lord, Stephen C. West, Ivan Ahel, Dragana Ahel, J. Ross Chapman, Sebastian Deindl, Simon J. Boulton
Summary: The loss of ALC1 increases sensitivity to PARP inhibitors, indicating the importance of nucleosome remodeling in DNA repair. ALC1 deficiency is synthetically lethal with homologous recombination deficiency, due to chromosome instability caused by unrepaired DNA gaps.
Biographical-Item
Multidisciplinary Sciences
Stephen C. West, Stephen C. Kowalczykowski
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Review
Biochemistry & Molecular Biology
Sarah J. Young, Stephen C. West
Summary: SLX4 serves as a molecular scaffold for the assembly of multiple protein complexes involved in DNA repair and genome stability maintenance. The interaction between SLX4 and MutS beta suggests a common role in promoting DNA maintenance.
CRITICAL REVIEWS IN BIOCHEMISTRY AND MOLECULAR BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Kasper Fugger, Ilirjana Bajrami, Mariana Silva Dos Santos, Sarah Jane Young, Simone Kunzelmann, Geoff Kelly, Graeme Hewitt, Harshil Patel, Robert Goldstone, Thomas Carell, Simon J. Boulton, James MacRae, Ian A. Taylor, Stephen C. West
Summary: Mutations in BRCA1 or BRCA2 genes increase the risk of breast and ovarian cancer, but inhibiting DNPH1 can enhance the sensitivity of BRCA-deficient cells to PARP inhibitors. Targeting DNPH1 provides a promising strategy for hypersensitizing BRCA-deficient cancers to PARPi therapy.
Article
Multidisciplinary Sciences
Radhakrishnan Kanagaraj, Richard Mitter, Theodoros Kantidakis, Matthew M. Edwards, Anaid Benitez, Probir Chakravarty, Beiyuan Fu, Olivier Becherel, Fengtang Yang, Martin F. Lavin, Amnon Koren, Aengus Stewart, Stephen C. West
Summary: Mutations in the SETX gene are associated with progressive neurodegenerative diseases AOA2 and ALS4. Genomic and transcriptomic analysis of patient-derived cells and SETX knockout models revealed an increase in chromosomal instability, changes in gene-expression profiles, and the role of transcription stress in SETX mutationassociated chromosome fragility and AOA2.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Multidisciplinary Sciences
Han N. Ho, Stephen C. West
Summary: Holliday junctions (HJs) play a crucial role in homologous recombination and DNA repair, and their resolution is essential for proper chromosome segregation. We developed a method involving DNAzyme self-cleavage to generate DNA molecules containing single or double HJs for biochemical analysis. Our findings demonstrate that the BLM-TopIII alpha-RMI1-RMI2 complex can dissolve double HJs, while structure-selective endonucleases can resolve single or double HJs.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Cell Biology
Anaid Benitez, Marie Sebald, Radhakrishnan Kanagaraj, Monica C. Rodrigo-Brenni, Ying Wai Chan, Chih-Chao Liang, Stephen C. West
Summary: Our genomes contain common fragile sites (CFSs), which are difficult to replicate and cause genomic instability. Loss of GEN1, an endonuclease, reduces CFS expression, leading to defects in DNA synthesis, chromosome segregation, and DNA damage. This suggests that GEN1 plays a dual role in resolving both DNA replication and recombination intermediates.
Article
Multidisciplinary Sciences
Luke A. Greenhough, Chih-Chao Liang, Ondrej Belan, Simone Kunzelmann, Sarah Maslen, Monica C. Rodrigo-Brenni, Roopesh Anand, Mark Skehel, Simon J. Boulton, Stephen C. West
Summary: Homologous recombination is a vital process in life, involved in replication fork protection, DNA repair, and genetic exchange. Mutations in key recombination genes increase the risk of various cancers and Fanconi anemia. The RAD51 paralogues, including RAD51B, RAD51C, RAD51D, and XRCC2, play important roles in these processes, as demonstrated by their structure and function in the RAD51B-RAD51C-RAD51D-XRCC2 complex (BCDX2). BCDX2 stimulates RAD51 filament formation for recombinational DNA repair, crucial for tumor avoidance.
Article
Chemistry, Multidisciplinary
Huadong Jiang, Nannan Kong, Zeyuan Liu, Stephen C. West, Ying Wai Chan
Summary: Chromatin bridges between daughter nuclei during cell division can lead to DNA damage and chromosomal rearrangements. ANKLE1, a human endonuclease, accumulates at the midbody and prevents DNA damage and autoimmunity by cleaving chromatin bridges. ANKLE1 acts by priming the nucleolytic activity of TREX1 and inhibiting the formation of micronuclei and cytosolic dsDNA. This study highlights the importance of ANKLE1 in maintaining genomic stability and preventing autoimmune responses.
Review
Oncology
Kasper Fugger, Graeme Hewitt, Stephen C. West, Simon J. Boulton
Summary: HRD tumors, especially those with BRCA mutations, are sensitive to PARPis but can develop resistance through reversion mutations or genetic/epigenetic alterations. Targeting novel genes identified from genetic screens may help overcome PARPi resistance and improve treatment efficacy for HRD cancers.
