Article
Multidisciplinary Sciences
Sonia Jimeno, Rosario Prados-Carvajal, Maria Jesus Fernandez-Avila, Sonia Silva, Domenico Alessandro Silvestris, Martin Endara-Coll, Judit Domingo-Prim, Fernando Mejias-Navarro, Guillermo Rodriguez-Real, Amador Romero-Franco, Silvia Jimeno-Gonzalez, Sonia Barroso, Valeriana Cesarini, Andres Aguilera, Angela Gallo, Neus Visa, Pablo Huertas
Summary: Specific RNA-related factors, including the RNA-editing enzyme ADAR2, play important roles in DNA repair. The researchers found that RNA editing is involved in the response to DNA damage, with a phenomenon called the RNA Editing DAmage Response (REDAR) being observed. REDAR relies on the checkpoint kinase ATR and the recombination factor CtIP, and depletion of ADAR2 leads to increased cellular sensitivity to genotoxic agents and impaired homologous recombination.
NATURE COMMUNICATIONS
(2021)
Article
Medicine, Research & Experimental
Edward Grimley, Alexander J. Cole, Thong T. Luong, Stacy C. McGonigal, Sarah Sinno, Dongli Yang, Kara A. Bernstein, Ronald J. Buckanovich
Summary: The study demonstrated that ALDHi can induce DNA double strand breaks in cancer cells and synergize with inhibitors of the ATM/ATR pathway. ALDHi can be used in conjunction with inhibitors of the ATM and ATR pathways, potentially offering a novel therapeutic approach to target HR-proficient ovarian cancer cells.
Review
Oncology
Lindsey Carlsen, Wafik S. El-Deiry
Summary: DNA damage response inhibitors are effective anti-cancer agents that sensitize tumor cells to radiotherapy and chemotherapy while also stimulating immune responses. However, the contribution of different inhibitors and genetic aberrations in cancers to immune mechanisms is not well-characterized, limiting the optimization of treatment regimens.
FRONTIERS IN ONCOLOGY
(2022)
Review
Cell Biology
Carlo Rinaldi, Paolo Pizzul, Maria Pia Longhese, Diego Bonetti
Summary: DNA transcription and replication are essential physiological processes, but they can pose a threat to genome integrity when competing for the same DNA substrate. R-loop structures can play important roles in normal physiological functions, but may lead to DNA damage and genome instability when their homeostasis is altered. Research has made progress in understanding R-loop regulation, but more studies are needed to fully comprehend their impact on genome stability and the cellular response to their formation.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Rodolfo Bortolozo Serafim, Cibele Cardoso, Vanessa Cristina Arfelli, Valeria Valente, Leticia Frohlich Archangelo
Summary: PIMREG expression is strongly related to cellular proliferation in malignant and normal cells. It is highly expressed in the central nervous system during embryo development and has been found to be elevated in various types of tumors. The expression level of PIMREG can serve as a biomarker for glioma progression and patient outcome. Additionally, it plays a role in DNA damage response and temozolomide resistance in glioblastoma cells.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2022)
Editorial Material
Biochemistry & Molecular Biology
William G. Dunphy
Summary: Frattini et al. (2021) demonstrate that TopBP1 forms phase-separated nuclear condensates to promote activation of ATR in cells experiencing genomic stress.
Article
Biochemistry & Molecular Biology
Stavroula Tsaridou, Georgia Velimezi, Frances Willenbrock, Maria Chatzifrangkeskou, Waheba Elsayed, Andreas Panagopoulos, Dimitris Karamitros, Vassilis Gorgoulis, Zoi Lygerou, Vassilis Roukos, Eric O'Neill, Dafni Eleftheria Pefani
Summary: This study identified a novel role for the tumor suppressor RASSF1A at rDNA break sites, providing mechanistic insight into how the DNA damage response is organized in a chromatin context and further evidence for how silencing of the RASSF1A tumor suppressor contributes to genome instability.
Article
Biochemistry & Molecular Biology
Chloe Gulliver, Ralf Hoffmann, George S. Baillie
Summary: The DNA damage response is crucial for maintaining genomic integrity and is often hijacked by cancer cells. Targeting ATM and ATR can enhance the treatment of prostate cancer and reduce therapeutic resistance.
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY
(2022)
Article
Cell Biology
Jennifer Q. J. Zhang, Sayanthooran Saravanabavan, Gopala K. Rangan
Summary: The DNA damage response pathway is upregulated in autosomal dominant polycystic kidney disease (ADPKD), but reducing the ATM kinase may only have short-term effects on reducing renal cell proliferation and does not alter the chronic progression of cystic kidney disease in vivo. This suggests that the DDR kinase ATM is dispensable for kidney cyst formation in ADPKD.
Article
Chemistry, Multidisciplinary
Di Xin, Xiaochen Gai, Yidi Ma, Zexing Li, Qilin Li, Xiaochun Yu
Summary: In response to genotoxic stress-induced DNA damage, TopBP1 plays a key role in ATR activation for signaling transduction and DNA damage repair. The study reveals that TopBP1 interacts with pre-ribosomal RNA (pre-rRNA) and colocalizes with it at DNA double-strand breaks (DSBs). The BRCT4-5 domain of TopBP1 recognizes pre-rRNA and undergoes liquid-liquid phase separation (LLPS) with it, which may be responsible for the formation of TopBP1 foci at DSBs. The inhibition of pre-rRNA synthesis impairs TopBP1-mediated cell cycle checkpoint activation and homologous recombination repair.
Review
Cell Biology
Jessica L. Hopkins, Li Lan, Lee Zou
Summary: Defects in DNA repair and damage signaling pathways contribute to genomic instability and impact tumorigenesis and treatment outcomes. Exploiting these defects can lead to therapeutic strategies, while also considering the implications for targeted therapy and immunotherapy.
GENES & DEVELOPMENT
(2022)
Article
Cell Biology
Foon Wu-Baer, Madeline Wong, Lydia Tschoe, Chyuan-Sheng Lin, Wenxia Jiang, Shan Zha, Richard Baer
Summary: Homology-directed repair (HDR) of double-strand DNA breaks (DSBs) relies on the enzymatic resection of DNA ends by CtIP/Sae2 protein, with ATM/ATR phosphorylation enhancing DNA resection but not essential for animal development.
Article
Pharmacology & Pharmacy
Fangfang Wang, Sora Jin, Franklin Mayca Pozo, Danmei Tian, Xiyang Tang, Yi Dai, Xinsheng Yao, Jinshan Tang, Youwei Zhang
Summary: The study identifies shikonin as an inhibitor that suppresses DNA damage response (DDR) activated by chemotherapeutic drugs in cancer cells. It inhibits DDR signal activation through the degradation of ATM and ATR-interacting protein (ATRIP), the upstream regulators of DDR. These findings reveal shikonin as a pan DDR inhibitor and identify ATM as a primary factor in determining the chemo sensitizing effect of shikonin.
ACTA PHARMACEUTICA SINICA B
(2022)
Article
Virology
Barbora Lubyova, Eva Tikalova, Kristyna Krulova, Jan Hodek, Ales Zabransky, Ivan Hirsch, Jan Weber
Summary: The molecular connection between the host DDR pathway and HBV replication has been demonstrated, with the roles of ATM and ATR PI3-kinases in HBc phosphorylation investigated. Etoposide and hydrogen peroxide treatment activated the ATM-Chk2 pathway, leading to increased phosphorylation of HBc and potential growth advantage to the replicating virus.
Article
Virology
Jared R. Erickson, Robert F. Kalejta, Paul D. Friesen
Summary: Multiplication of the invertebrate DNA baculoviruses activates the host DNA damage response (DDR), which promotes virus DNA replication. ATM, the key kinase in the host DNA damage response, was thought to play a critical role. However, this study found that baculoviruses can activate the host DNA damage response in an ATM-independent manner.
JOURNAL OF VIROLOGY
(2022)