Article
Multidisciplinary Sciences
Eva L. Morozko, Charlene Smith-Geater, Alejandro Mas Monteys, Subrata Pradhan, Ryan G. Lim, Peter Langfelder, Marketta Kachemov, Austin Hill, Jennifer T. Stocksdale, Pieter R. Cullis, Jie Wu, Joseph Ochaba, Ricardo Miramontes, Anirban Chakraborty, Tapas K. Hazra, Alice Lau, Sophie St-Cyr, Iliana Orellana, Lexi Kopan, Keona Q. Wang, Sylvia Yeung, Blair R. Leavitt, Jack C. Reidling, X. William Yang, Joan S. Steffan, Beverly L. Davidson, Partha S. Sarkar, Leslie M. Thompson
Summary: This study reveals the involvement of PIAS1 in DNA damage repair pathways and its connection with transcriptional modulation in neurodegenerative diseases. Knockdown of PIAS1 in HD mice normalizes transcriptional dysregulation and DNA damage repair mechanisms, impacting genomic integrity in neurons. The findings highlight the role of SUMO modifying machinery in DNA damage repair responses and transcriptional modulation in the context of neurodegenerative disease.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Review
Oncology
Antti Kukkula, Veera K. Ojala, Lourdes M. Mendez, Lea Sistonen, Klaus Elenius, Maria Sundvall
Summary: The SUMO pathway plays a crucial role in regulating cancer cell properties, and inhibition of this pathway shows promise as a potential therapeutic option for cancer treatment.
Article
Biochemistry & Molecular Biology
Julio C. Y. Liu, Ulrike Kuhbacher, Nicolai B. Larsen, Nikoline Borgermann, Dimitriya H. Garvanska, Ivo A. Hendriks, Leena Ackermann, Peter Haahr, Irene Gallina, Claire Guerillon, Emma Branigan, Ronald T. Hay, Yoshiaki Azuma, Michael Lund Nielsen, Julien P. Duxin, Niels Mailand
Summary: The study reveals that the SUMO-targeted ubiquitin ligase RNF4 plays a major role in ubiquitylation and proteasomal clearance of SUMOylated DPCs in the absence of DNA replication. SUMO modifications of DPCs do not affect their rapid degradation during DNA replication, but provide a critical salvage mechanism to remove DPCs formed after replication. The absence of the SUMO-RNF4 pathway leads to accumulation of unresolved DPCs, causing defective chromosome segregation and cell death during mitosis.
Review
Biochemistry & Molecular Biology
Antonio Galarreta, Pablo Valledor, Oscar Fernandez-Capetillo, Emilio Lecona
Summary: Post-translational modification of the DNA replication machinery by ubiquitin and SUMO plays key roles in ensuring the faithful duplication of genetic information. Ubiquitination and SUMOylation not only serve as signals for the extraction of factors from chromatin, but also mediate the disassembly of the replisome and preserve genomic stability in DNA replication.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Doohyung Lee, Katja Apelt, Seong-Ok Lee, Hsin-Ru Chan, Martijn S. Luijsterburg, Justin W. C. Leung, Kyle M. Miller
Summary: The inability to repair DNA double-strand breaks (DSBs) can lead to genome instability and human diseases, such as cancer. This study identifies zinc-finger proteins ZMYM2 and ZMYM3 as antagonizers of 53BP1 recruitment, which enhances the recruitment and function of HR proteins in DNA repair. Depletion of these proteins leads to genome instability, increased sensitivity to PARP inhibitors and ionizing radiation, and reduced HR repair.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Alana Sherker, Natasha Chaudhary, Salome Adam, Anne Margriet Heijink, Sylvie M. Noordermeer, Amelie Fradet-Turcotte, Daniel Durocher
Summary: The study reveals that Rap80 plays a redundant role in promoting BRCA1 recruitment to DNA damage sites, while RNF8 and RNF168 are also crucial in this process. The E3 ligase activity of BRCA1 is essential for recognizing ubiquitylated histone H2A Lys13/Lys15 in the absence of Rap80. The BRCA1 RING domain may facilitate nucleosome recognition in ways beyond promoting ubiquitylation.
Article
Biochemistry & Molecular Biology
Samuel R. Witus, Lisa M. Tuttle, Wenjing Li, Alex Zelter, Meiling Wang, Klaiten E. Kermoade, Damien B. Wilburn, Trisha N. Davis, Peter S. Brzovic, Weixing Zhao, Rachel E. Klevit
Summary: BRCA1/BARD1 is a tumor suppressor gene with functions in DNA damage repair and transcriptional regulation. It interacts with nucleosomes and facilitates ubiquitylation of histone H2A. Our study reveals novel interactions involving an intrinsically disordered DNA-binding region of BARD1 that support H2A ubiquitylation and recruitment to chromatin and DNA damage sites. These interactions contribute to cell survival and identify a network of BARD1-nucleosome interactions on chromatin.
Article
Medicine, General & Internal
Malgorzata Galecka, Janusz Szemraj, Kuan-Pin Su, Angelos Halaris, Michael Maes, Aleksandra Skiba, Piotr Galecki, Katarzyna Blizniewska-Kowalska
Summary: This study found that there is increased expression of JAK3 and decreased expression of STAT1 in depressed patients.
JOURNAL OF CLINICAL MEDICINE
(2022)
Review
Dermatology
Qi Yin, Albert Wolkerstorfer, Oren Lapid, Frank B. Niessen, Paul P. M. Van Zuijlen, Susan Gibbs
Summary: Keloid tissues contain inflammatory cells and upregulated pro-inflammatory cytokines. The Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway mediate cellular responses to these cytokines. Preclinical studies indicate a role for the JAK-STAT pathway in keloid pathogenesis and a potential role for JAK-STAT inhibitors in keloid treatment. Further investigation on relevant biomarkers in a human keloid skin model and in clinical studies is needed.
EXPERIMENTAL DERMATOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Ines Roger, Javier Milara, Paula Montero, Julio Cortijo
Summary: Pulmonary hypertension is a group of diseases characterized by an increase in pulmonary vascular resistance, leading to right ventricular failure and premature death. Current treatments for PH are limited to vasodilatory agents, prompting the search for new drugs that target pulmonary artery remodeling. Activation of the JAK/STAT pathway plays a critical role in pulmonary artery remodeling and PH progression, suggesting it as a potential target for future treatments.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Obstetrics & Gynecology
Hiroaki Inui, Takako Kawakita, Misaki Murayama, Tomotaka Nakagawa, Hikari Sasada, Ayaka Shinohara, Ryousuke Aragaki, Tomohiro Kagawa, Yuri Kadota, Takeshi Kato, Masato Nishimura, Takeshi Iwasa
Summary: STAT inhibitors have a therapeutic effect on endometriosis.
REPRODUCTIVE SCIENCES
(2023)
Article
Biochemical Research Methods
Chongyang Li, Alison Boutet, Cristina Mirela Pascariu, Trent Nelson, Mathieu Courcelles, Zhaoguan Wu, Simon Comtois-Marotte, Gregory Emery, Pierre Thibault
Summary: Protein inhibitor of activated STAT (PIAS) proteins are E3 SUMO ligases that play important roles in protein stability and signaling transduction pathways. In this study, quantitative SUMO proteomics was used to investigate the regulatory role of PIAS SUMO E3 ligases in cell proliferation and cell cycle. The results reveal novel insights into both the redundant and specific regulatory mechanisms of PIAS SUMO E3 ligases.
JOURNAL OF PROTEOME RESEARCH
(2023)
Review
Biochemistry & Molecular Biology
Jia Liu, Faping Wang, Fengming Luo
Summary: There are four members of the JAK family and seven of the STAT family in mammals. The JAK/STAT molecular pathway can be activated by various hormones, cytokines, growth factors, etc. The JAK/STAT signaling pathway extensively mediates various biological processes such as cell proliferation, differentiation, migration, apoptosis, and immune regulation.
Article
Cell Biology
Zhihui Min, Jiebai Zhou, Ruolin Mao, Bo Cui, Yunfeng Cheng, Zhihong Chen
Summary: The study found that PQQ can alleviate allergic airway inflammation in mice by improving the immune microenvironment and regulating the JAK-STAT signaling pathway, suggesting its potential as a therapeutic agent for inflammatory diseases, including asthma.
MEDIATORS OF INFLAMMATION
(2022)
Review
Cell Biology
Rodrigo Martin-Rufo, Guillermo de la Vega-Barranco, Emilio Lecona
Summary: This article discusses the mechanisms used by ubiquitin/SUMO and VCP/p97 to establish molecular timers throughout DNA replication and their significance in maintaining genome stability.
SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Joanna R. Morris, Alexander J. Garvin
JOURNAL OF MOLECULAR BIOLOGY
(2017)
Review
Biology
Alexander J. Garvin, Joanna R. Morris
PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES
(2017)
Article
Cell Biology
Ruth M. Densham, Joanna R. Morris
Article
Multidisciplinary Sciences
Michael Uckelmann, Ruth M. Densham, Roy Baas, Herrie H. K. Winterwerp, Alexander Fish, Titia K. Sixma, Joanna R. Morris
NATURE COMMUNICATIONS
(2018)
Article
Biochemistry & Molecular Biology
Anastasios Spiliotopoulos, Lia Blokpoel Ferreras, Ruth M. Densham, Simon G. Caulton, Ben C. Maddison, Joanna R. Morris, James E. Dixon, Kevin C. Gough, Ingrid Dreveny
JOURNAL OF BIOLOGICAL CHEMISTRY
(2019)
Article
Cell Biology
Alexander J. Garvin, Alexandra K. Walker, Ruth M. Densham, Anoop Singh Chauhan, Helen R. Stone, Hannah L. Mackay, Mohammed Jamshad, Katarzyna Starowicz, Manuel Daza-Martin, George E. Ronson, Alexander J. Lanz, James F. Beesley, Joanna R. Morris
GENES & DEVELOPMENT
(2019)
Article
Biochemistry & Molecular Biology
Alexander J. Garvin, Ahmed H. A. Khalaf, Alessandro Rettino, Jerome Xicluna, Laura Butler, Joanna R. Morris, David M. Heery, Nicole M. Clarke
NUCLEIC ACIDS RESEARCH
(2019)
Article
Multidisciplinary Sciences
Manuel Daza-Martin, Katarzyna Starowicz, Mohammed Jamshad, Stephanie Tye, George E. Ronson, Hannah L. MacKay, Anoop Singh Chauhan, Alexandra K. Walker, Helen R. Stone, James F. J. Beesley, Jennifer L. Coles, Alexander J. Garvin, Grant S. Stewart, Thomas J. McCorvie, Xiaodong Zhang, Ruth M. Densham, Joanna R. Morris
Review
Cell Biology
Stephanie Tye, George E. Ronson, Joanna R. Morris
Summary: The protection of stalled DNA replication forks requires the coordination of multiple recombination proteins and the utilization of nucleases in a different way than in homologous recombination. Despite similarities, the protection mechanism at stalled forks has unique features compared to the RAD51 loading step in homologous recombination.
SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY
(2021)
Editorial Material
Biochemistry & Molecular Biology
Joanna R. Morris
Summary: New findings show that BARD1, a partner of BRCA1, plays a crucial role in positioning the E2 ubiquitin-conjugating enzyme and promoting DNA damage-induced chromatin recruitment, enhancing the function of BRCA1.
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2021)
Article
Cell Biology
Emma L. Faulkner, Jeremy A. Pike, Ruth M. Densham, Evelyn Garlick, Steven G. Thomas, Robert K. Neely, Joanna R. Morris
Summary: Expansion microscopy (ExM) enables the investigation of nanoscale nuclear processes by overcoming the limitations of traditional microscopy techniques and allowing quantitative description of 3D nanoscale structures.
JOURNAL OF CELL SCIENCE
(2022)
Article
Multidisciplinary Sciences
Alexander J. Garvin, Alexander J. Lanz, Joanna R. Morris
Summary: In this study, the specificity and sensitivity of twenty-four anti-SUMO monoclonal antibodies towards monomeric and polymeric SUMO1-4 were tested in various detection formats. Significant variability was observed between the antibodies for different conjugation states, stress responses, and enrichment assays. It was found that all four anti-SUMO4 monoclonal antibodies tested cross-reacted with SUMO2/3, and several SUMO2/3 antibodies cross-reacted with SUMO4.
SCIENTIFIC REPORTS
(2022)
Article
Biochemistry & Molecular Biology
Marium Rana, Alessio Perotti, Lucy M. Bisset, James D. Smith, Emma Lamden, Zahra Khan, Media K. Ismail, Katherine Ellis, Katie A. Armstrong, Samantha L. Hodder, Cosetta Bertoli, Leticia Meneguello, Robertus A. M. de Bruin, Joanna R. Morris, Isolda Romero-Canelon, James H. R. Tucker, Nikolas J. Hodges
Summary: In this study, a new nucleoside analogue, 1-(S,R-p), was found to be cytotoxic to gemcitabine-resistant pancreatic ductal adenocarcinoma (PDAC) cells, by inhibiting DNA replication and arresting cell cycle at S-phase, as observed directly through DNA-fibre fluorography. Moreover, the compound was shown to activate several genes and downstream targets related to DNA replication and cell cycle regulation. These findings suggest that 1-(S,R-p) can be a promising candidate for the development of new treatments for PDAC.
Article
Oncology
Manuel Daza-Martin, Ruth M. Densham, Joanna R. Morris
MOLECULAR & CELLULAR ONCOLOGY
(2019)
Review
Biochemistry & Molecular Biology
Ruth M. Densham, Joanna R. Morris
FRONTIERS IN MOLECULAR BIOSCIENCES
(2019)