Article
Cell Biology
Md Akram Hossain, Yunfeng Lin, Garrett Driscoll, Jia Li, Anne McMahon, Joshua Matos, Haichao Zhao, Daisuke Tsuchimoto, Yusaku Nakabeppu, Jianjun Zhao, Shan Yan
Summary: APE2 is essential for activating the ATR DDR pathway in response to various stressful conditions in Xenopus laevis egg extracts and human pancreatic cancer cells. Inhibition of APE2 leads to increased DNA damage and sensitizes cancer cells to chemotherapy drugs, indicating its crucial role in maintaining genome integrity.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Immunology
Daniel de Oliveira Patricio, Greicy Brisa Malaquias Dias, Lucilene Wildner Granella, Ben Trigg, Helena Claire Teague, Dina Bittencourt, Andre Bafica, Alfeu Zanotto-Filho, Brian Ferguson, Daniel Santos Mansur
Summary: DNA-PKcs plays a role in restricting the spread of Zika virus infection in human cells by influencing the transcription of interferons and related genes. This mechanism is independent of DNA breaks.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Zhong-Xuan Wang, Yi Liu, Yao-Lin Li, Qiao Wei, Rong-Rong Lin, Ruiqing Kang, Yang Ruan, Zhi-Hao Lin, Nai-Jia Xue, Bao-Rong Zhang, Jia-Li Pu
Summary: DNA damage and defective DNA repair are implicated in neurodegeneration of Parkinson's disease. The study shows that the protein DJ-1 plays a crucial role in modulating DNA double-strand break repair by promoting both homologous recombination and nonhomologous end joining. DJ-1 interacts with PARP1 and enhances its enzymatic activity during DNA repair. Importantly, PD patients with DJ-1 mutation have impaired PARP1 activity and DSB repair.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Li-Kuang Tsai, Min Peng, Chia-Chun Chang, Luan Wen, Lin Liu, Xiubin Liang, Y. Eugene Chen, Jie Xu, Li-Ying Sung
Summary: This study reveals that ZSCAN4 promotes DNA repair in mESCs by interacting with PARP1 and reducing DSB. PARP1 binds directly to ZSCAN4, with the second α-helix and the fourth zinc finger motif of ZSCAN4 playing a critical role in this interaction.
CELL AND BIOSCIENCE
(2023)
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
Michelle L. Swift, Kate Beishline, Samuel Flashner, Jane Azizkhan-Clifford
Summary: This passage discusses the role of Sp1 in the cell cycle and its regulation of DSB repair pathway choice, favoring NHEJ repair. Sp1 is shown to recruit the NHEJ repair factor 53BP1 in G1 phase, while being evicted through phosphorylation in S phase, inhibiting HR repair.
Article
Biochemistry & Molecular Biology
Xiaopeng Lu, Min Xu, Qian Zhu, Jun Zhang, Ge Liu, Yantao Bao, Luo Gu, Yuan Tian, He Wen, Wei-Guo Zhu
Summary: Histone methyltransferase KMT5A interacts with E3 ligases RNF8 and RNF168 to establish histone modification status for DNA damage repair. KMT5A increases H4K20 monomethylation at DSBs and enhances RNF168's activity in catalyzing H2A ubiquitination, linking the two processes. The interaction between H2A acidic patch and KMT5A residues R188/R189 is crucial for KMT5A-mediated regulation of H2A ubiquitination.
Article
Biochemistry & Molecular Biology
Sijie Liu, Yu Hua, Jingna Wang, Lingyan Li, Junjie Yuan, Bo Zhang, Ziyang Wang, Jianguo Ji, Daochun Kong
Summary: Protection of 30 overhangs in DNA double-strand breaks (DSBs) repair is achieved through the transient formation of RNA-DNA hybrids, with RNA polymerase III (RNAPIII) responsible for synthesizing the RNA strand. CtIP and MRN nuclease activity are required for initiating RNAPIII-mediated RNA synthesis at DSBs. Reduced RNAPIII levels suppress homologous recombination (HR) and lead to genetic loss > 30 bp at DSBs.
Article
Multidisciplinary Sciences
Liat Stoler-Barak, Ethan Harris, Ayelet Peres, Hadas Hezroni, Mirela Kuka, Pietro Di Lucia, Amalie Grenov, Neta Gurwicz, Meital Kupervaser, Bon Ham Yip, Matteo Iannacone, Gur Yaari, John D. Crispino, Ziv Shulman
Summary: The protein kinase DYRK1A is essential for B cell-mediated protection from viral infection and effective vaccination by regulating class switch recombination (CSR). It plays a crucial role in B cell immune responses, including attenuating B cell proliferation and promoting the production of pathogen-eliminating antibodies.
NATURE COMMUNICATIONS
(2023)
Article
Cell Biology
Qian Chen, Kai Ma, Xiuhua Liu, Shih-Hsun Chen, Peng Li, Yonghao Yu, Anthony K. L. Leung, Xiaochun Yu
Summary: In this study, truncated PARP1 (tPARP1) was found to interact with the RNA polymerase III (Pol III) complex in the cytosol during apoptosis. tPARP1 was shown to facilitate the mono-ADP-ribosylation of RNA Pol III and contribute to IFN-beta production and apoptosis. Inhibiting PARP1 or expressing the non-cleavable form of PARP1 resulted in impairment of these molecular events.
Article
Oncology
Xu Zhao, Yuan Ma, Jing Li, Xuanzi Sun, Yuchen Sun, Fengyi Qu, Xiaobo Shi, Yuchen Xie, Siqi Liu, Yanfang Ma, Chao Ji, Weibin Hu, Shaomin Che, Xiaozhi Zhang
Summary: The overexpression of AEG-1 in esophageal squamous cell carcinoma (ESCC) plays a crucial role in radioresistance by recruiting the deubiquitinase USP10 to promote DNA damage repair, leading to increased radioresistance. These findings provide potential therapeutic targets to enhance the efficacy of radiotherapy in ESCC.
Article
Multidisciplinary Sciences
Nicholas A. W. Bell, Philip J. Haynes, Katharina Brunner, Taiana Maia de Oliveira, Maria M. Flocco, Bart W. Hoogenboom, Justin E. Molloy
Summary: PARP1 binds and condenses undamaged DNA by stabilizing DNA loops, and blocks condensation reversal for damaged DNA in the presence of NAD(+), suggesting a mechanism for PARP1 in the organization of chromatin structure.
Article
Biochemistry & Molecular Biology
Rebekka Kitzinger, Gerhard Fritz, Christian Henninger
Summary: Rho GTPases like RAC1 are molecular switches that trigger signal transduction pathways in response to extracellular stimuli. This study investigates the role of RAC1 in the doxorubicin-induced DNA damage response (DDR). Silencing RAC1 and manipulating its nuclear localization reveal that RAC1 is required for a substantial activation of DDR, and balanced levels of active/inactive RAC1 inside the nucleus are crucial for this response.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
(2022)
Article
Multidisciplinary Sciences
Sarah M. Morgan, Hideki Tanizawa, Lisa Beatrice Caruso, Michael Hulse, Andrew Kossenkov, Jozef Madzo, Kelsey Keith, Yinfei Tan, Sarah Boyle, Paul M. Lieberman, Italo Tempera
Summary: This study demonstrates the essential role of PARP1 in regulating the chromatin structure and gene expression of EBV. PARP inhibition leads to decreased intragenomic interactions within the EBV episome, but also forms new chromatin loops. Additionally, PARP inhibition alters the binding of chromatin looping factor CTCF and gene expression.
NATURE COMMUNICATIONS
(2022)
Article
Biology
Erwan Goy, Maxime Tomezak, Caterina Facchin, Nathalie Martin, Emmanuel Bouchaert, Jerome Benoit, Clementine de Schutter, Joe Nassour, Laure Saas, Claire Drullion, Priscille M. Brodin, Alexandre Vandeputte, Olivier Molendi-Coste, Laurent Pineau, Gautier Goormachtigh, Olivier Pluquet, Albin Pourtier, Fabrizio Cleri, Eric Lartigau, Nicolas Penel, Corinne Abbadie
Summary: Induction of second primary cancers is a rare but severe complication of curative-intent radiation therapy. Research shows that normal human or mouse dermal fibroblasts exposed to out-of-field radiation dose at the margin of the target volume do not die, but enter a long-lived senescent state, leading to the accumulation of unrepaired DNA single-strand breaks. Some of these senescent cells eventually escape cell cycle arrest and give rise to daughter cells with mutations and invasive properties. This discovery highlights the role of single-strand break-induced senescence as the mechanism of second primary cancer initiation, with potential implications for prevention.
Article
Oncology
Rumana N. Hussain, Sarah E. Coupland, Jakub Khzouz, Helen Kalirai, Jason L. Parsons
Review
Biochemistry & Molecular Biology
Gabrielle J. Grundy, Jason L. Parsons
GUARDIANS OF THE GENOME: DNA DAMAGE AND REPAIR
(2020)
Article
Oncology
Eirini Terpsi Vitti, Andrzej Kacperek, Jason L. Parsons
Review
Biochemistry & Molecular Biology
Jonathan R. Hughes, Jason L. Parsons
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2020)
Article
Cell Biology
Rachael E. Clifford, Naren Govindarajah, David Bowden, Paul Sutton, Mark Glenn, Mahnaz Darvish-Damavandi, Simon Buczacki, Ultan McDermott, Zdzislaw Szulc, Besim Ogretmen, Jason L. Parsons, Dale Vimalachandran
Article
Oncology
Catherine M. Nickson, Maria Rita Fabbrizi, Rachel J. Carter, Jonathan R. Hughes, Andrzej Kacperek, Mark A. Hill, Jason L. Parsons
Summary: Ionizing radiation induces DNA damage leading to cell death. The biological effects of high-LET IR are not well understood, but USP9X plays a crucial role in cell survival post high-LET radiation by stabilizing proteins involved in centrosome formation.
FRONTIERS IN ONCOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Maria Rita Fabbrizi, Jason L. Parsons
Summary: This article provides an up-to-date review on the radiobiological effects of RT in HNSCC cell models, focusing on specific cell death mechanisms, and details some of the current therapeutic strategies to enhance the radiosensitivity of HNSCC cells.
EXPERT REVIEWS IN MOLECULAR MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Julie Bourseguin, Wen Cheng, Emily Talbot, Liana Hardy, Jenny Lai, Ailsa M. Jeffries, Michael A. Lodato, Eunjung Alice Lee, Svetlana Khoronenkova
Summary: ATM deficiency in Ataxia-telangiectasia can result in DNA damage and dysfunction of immune cell microglia, leading to neurodegeneration.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Sifaddin M. R. Konis, Jonathan R. Hughes, Jason L. Parsons
Summary: TRIM26 plays a central role in determining the response to different forms of oxidative stress by regulating DNA glycosylase levels required for an efficient base excision repair (BER) response.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Oncology
Rhianna M. Hill, Sonia Rocha, Jason L. Parsons
Summary: Hypoxia, a common phenomenon in tumors, leads to increased resistance to radiotherapy and poor prognosis for patients. Overcoming hypoxia within tumors by developing new therapeutic techniques in combination with radiotherapy is crucial for improving patient survival. This review provides an up-to-date overview of how hypoxia contributes to radioresistance in head and neck cancer and discusses strategies to overcome this challenge.
Article
Oncology
Massimiliano Mellone, Klaudia Piotrowska, Giulia Venturi, Lija James, Aleksandra Bzura, Maria A. Lopez, Sonya James, Chuan Wang, Matthew J. Ellis, Christopher J. Hanley, Josephine F. Buckingham, Kerry L. Cox, Gareth Hughes, Viia Valge-Archer, Emma King, Stephen A. Beers, Vincent Jaquet, George D. D. Jones, Natalia Savelyeva, Emre Sayan, Jason L. Parsons, Stephen Durant, Gareth J. Thomas
Summary: Myofibroblastic cancer-associated fibroblast (myoCAF)-rich tumors have low T cell infiltration and poor response to immune-checkpoint blockade. This study identifies ATM as a central regulator of myoCAF differentiation, providing a potential therapeutic target for overcoming immunotherapy resistance in myoCAF-rich tumors.
Review
Biochemistry & Molecular Biology
Beth Wilkinson, Mark A. A. Hill, Jason L. L. Parsons
Summary: Radiotherapy using ionising radiation is a common treatment for many cancers, as it damages the DNA of cancer cells. Complex DNA damage (CDD), which is difficult to repair, is a key contributor to the cell-killing effects of radiotherapy. The level and complexity of CDD increase with higher ionisation density of the radiation. Detecting and measuring IR-induced CDD in cells and tissues poses challenges, and there are uncertainties regarding the specific DNA repair mechanisms involved. However, advancements are being made in these areas to improve understanding of cellular responses to CDD and explore targeted therapies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Emma Melia, Jason L. Parsons
Summary: Radiotherapy is an important treatment for cancer, and particle radiotherapy offers advantages over conventional photons. Proton beam therapy and carbon ion radiotherapy can precisely target tumors and generate enhanced therapeutic responses. DNA damage plays a key role in tumor cell killing, and the complexity of DNA damage increases with radiation intensity. Understanding the DNA repair pathways activated by different radiation sources is crucial for improving the efficacy of radiotherapy.
BIOSCIENCE REPORTS
(2023)
Article
Biochemical Research Methods
Maria Rita Fabbrizi, Jonathan R. Hughes, Jason L. Parsons
Summary: The comet assay is a sensitive method for detecting DNA damage, particularly single and double DNA strand breaks, in individual cells. By detecting specific DNA lesions and studying the repair of these lesions, the assay can provide important insights into the complexity of DNA damage induced by ionizing radiation and other genotoxic agents.
METHODS AND PROTOCOLS
(2021)
Article
Cell Biology
Jonathan R. Hughes, Jason L. Parsons
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2020)