Article
Biochemistry & Molecular Biology
Alexandra Vaisman, John P. McDonald, Mallory R. Smith, Sender L. Aspelund, Thomas C. Evans, Roger Woodgate
Summary: Y-family DNA polymerases consist of six phylogenetically separate subfamilies, with representatives found in all three domains of life. Different evolutionary diversity exists within eukaryotes, with different species possessing varying numbers and types of Y-family pols. The Y-family pols from Thermomyces lanuginosus show increased thermostability and share major biochemical properties with their human counterparts, displaying low fidelity during DNA synthesis.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2021)
Article
Multidisciplinary Sciences
Sabrina F. Mansilla, Agostina P. Bertolin, Sofia Venerus Arbilla, Bryan A. Castano, Tiya Jahjah, Jenny K. Singh, Sebastian O. Siri, Maria Victoria Castro, Maria Belen de la Vega, Annabel Quinet, Lisa Wiesmueller, Vanesa Gottifredi
Summary: Recent studies have shown that the choice of a DNA damage tolerance pathway involves competition between PrimPol-mediated repriming and fork reversal. Pol t plays a unique role in regulating this pathway choice, with Pol t deficiency leading to PrimPol-dependent repriming and accelerated DNA replication. However, this excessive participation of PrimPol in DNA elongation can trigger chromosome instability and replication stress signals in Pol t-depleted cells, revealing an unexpected role of Pol t in protecting genome stability.
Article
Chemistry, Multidisciplinary
Ying Tan, Su Guo, Jun Wu, Hua Du, Lin Li, Changjun You, Yinsheng Wang
Summary: This study investigated the transcriptional bypass of DNA lesions by TLS polymerases, specifically focusing on N-2-alkyl-dG lesions in HEK293T cells. The results showed that N-2-alkyl-dG lesions strongly blocked transcription and led to specific mutations, with Pol eta playing a crucial role in transcriptional bypass efficiency. Additionally, the repair of N-2-nBu-dG lesions was found to be less affected by genetic depletion of Pol eta or Rev1, highlighting the diverse functions of TLS DNA polymerases.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Biochemistry & Molecular Biology
Anudari Munkhjargal, Myung-Jin Kim, Da-Yeon Kim, Young-Jun Jeon, Young-Hoon Kee, Lark-Kyun Kim, Yong-Hwan Kim
Summary: The PML protein plays a critical role in regulating the ICL repair pathway, and its depletion can affect DNA damage responses and repair, leading to increased sensitivity of cells to mitomycin C. This study suggests that PML is essential for damage-induced CHK1 phosphorylation, which is important for FA gene expression and repairing ICLs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Oncology
Federica Martorana, Leandro Apolinario Da Silva, Cristiana Sessa, Ilaria Colombo
Summary: DNA damage leads to genome instability and increases cancer susceptibility. Targeted drugs against DNA repair, such as PARP inhibitors, have shown efficacy in various tumor types but also come with potential toxicities. Therefore, it is crucial to identify and manage adverse events of these drugs, especially in combination therapies.
Article
Chemistry, Multidisciplinary
Feng Tang, Yinan Wang, Zi Gao, Shiyuan Guo, Yinsheng Wang
Summary: This study reveals the interaction between DNA polymerase eta and DHX9 and demonstrates that this interaction promotes the replicative bypass of G4 structures in chromatin.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Biochemistry & Molecular Biology
Ruyuan Yu, Yameng Hu, Shuxia Zhang, Xincheng Li, Miaoling Tang, Meisongzhu Yang, Xingui Wu, Ziwen Li, Xinyi Liao, Yingru Xu, Man Li, Suwen Chen, Wanying Qian, Li-Yun Gong, Libing Song, Jun Li
Summary: In this study, the researchers found that DNA damage triggers the translation of a microprotein called DDUP, which helps to maintain repair complexes at damaged sites and initiate DNA damage repair mechanisms. Inhibition of DDUP by ATR inhibitor increases the sensitivity of cancer cells to DNA-damaging chemotherapeutics.
NUCLEIC ACIDS RESEARCH
(2022)
Review
Cell Biology
Priyanka Saha, Tanima Mandal, Anupam D. Talukdar, Deepak Kumar, Sanjay Kumar, Prem P. Tripathi, Qi-En Wang, Amit K. Srivastava
Summary: Inhibition of Pol eta polymerase may enhance sensitivity of cancer cells to chemotherapy, reduce drug-induced mutations, and prevent the development of secondary tumors. The Pol eta-mediated TLS mechanism has potential clinical implications in therapy, but there are still challenges and unknown factors that need to be addressed.
JOURNAL OF CELLULAR PHYSIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Gabriela Barszczewska-Pietraszek, Malgorzata Drzewiecka, Piotr Czarny, Tomasz Skorski, Tomasz Sliwinski
Summary: DNA polymerase theta (Pol theta)-mediated end joining (TMEJ) is a crucial mechanism for repairing DNA double-strand breaks (DSBs), and its inhibition has potential therapeutic value in cancer treatment. Pol theta has synthetic lethal interactions with other DNA repair mechanisms and is being studied as a target in cancer research. Different methods, including RNA interference and small molecule inhibitors, have been used to inhibit Pol theta. This review provides an overview of Pol theta and its role in DNA repair, discusses the current state of Pol theta inhibitors, and highlights the promise of Pol theta as a therapeutic target.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
Monica Ganzinelli, Federica Guffanti, Anna Ianza, Navid Sobhani, Sergio Crovella, Fabrizio Zanconati, Cristina Bottin, Marco Confalonieri, Stefano Fumagalli, Alessandra Guglielmi, Daniele Generali, Giovanna Damia
Summary: The study analyzed the correlation between DNA repair biomarkers and survival in malignant pleural mesothelioma (MPM) patients and found that down-regulation of DNA repair expression score is associated with longer survival. These findings could potentially lead to the development of a simple, cost-effective test for better management of MPM patients.
Review
Cell Biology
Luisa Maresca, Barbara Stecca, Laura Carrassa
Summary: Targeted therapies and immunotherapies have shown clinical benefits in melanoma patients, but resistance and relapse are common. This review discusses the potential of exploiting DNA damage response (DDR) as a therapeutic approach in melanoma. The use of DDR inhibitors, both as single agents and in combination with other therapies, shows promise in preclinical studies and ongoing clinical trials.
Article
Oncology
Fiifi Neizer-Ashun, Resham Bhattacharya
Summary: The DNA damage response relies on CHK1 kinase for maintaining genomic integrity, involving in processes such as DNA replication and mitotic progression. While CHK1 has potential in cancer therapy, it has yet to be fully realized clinically.
Article
Multidisciplinary Sciences
Yudong Zhang, Lingli Yuan
Summary: This study elucidates the regulatory mechanism of FLT3-ITD on CHK1 and reveals the correlation between high CHK1 level and lower survival rates in AML patients. Knockdown of CHK1 enhances the sensitivity of AML cells to epigenetic inhibitors, suggesting a potential therapeutic strategy for FLT3-ITD+AML.
SCIENTIFIC REPORTS
(2021)
Article
Biochemistry & Molecular Biology
Marie-Michelle Genois, Jean-Philippe Gagne, Takaaki Yasuhara, Jessica Jackson, Sneha Saxena, Marie-France Langelier, Ivan Ahel, Mark T. Bedford, John M. Pascal, Alessandro Vindigni, Guy G. Poirier, Lee Zou
Summary: Recent research has shown that CARM1 interacts with PARP1 at DNA replication forks, slowing fork speed and promoting the stress response mechanism of fork reversal.
Article
Biochemistry & Molecular Biology
Davi Jardim Martins, Jenny Kaur Singh, Tiya Jahjah, Alexandre Teixeira Vessoni, Giovana da Silva Leandro, Matheus Molina Silva, Denis Serge Francois Biard, Annabel Quinet, Carlos Frederico Martins Menck
Summary: Xeroderma pigmentosum (XP) variant cells deficient in Polη polymerase show increased sensitivity to UV radiation, affecting cell proliferation and migration. Polι may act as a backup for Polη in bypassing UV-induced photoproducts.
PHOTOCHEMISTRY AND PHOTOBIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Florencia Villafanez, Iris Alejandra Garcia, Sofia Carbajosa, Maria Florencia Pansa, Sabrina Mansilla, Maria Candelaria Llorens, Virginia Angiolini, Laura Guantay, Heinz Jacobs, Kevin P. Madauss, Israel Gloger, Vanesa Gottifredi, Jose Luis Bocco, Gaston Soria
Editorial Material
Cell Biology
Marina Alejandra Gonzalez Besteiro, Vanesa Gottifredi
JOURNAL OF CELL BIOLOGY
(2019)
Article
Biochemistry & Molecular Biology
Maria Belen Federico, Sebastian Omar Siri, Nicolas Luis Calzetta, Natalia Soledad Paviolo, Maria Belen de la Vega, Julieta Martino, Maria Carolina Campana, Lisa Wiesmueller, Vanesa Gottifredi
Review
Genetics & Heredity
Sabrina Florencia Mansilla, Maria Belen De la Vega, Nicolas Luis Calzetta, Sebastian Omar Siri, Vanesa Gottifredi
Editorial Material
Oncology
Vanesa Gottifredi, Lisa Wiesmueller
Review
Oncology
Agustina P. Bertolin, Jean-Sebastien Hoffmann, Vanesa Gottifredi
Article
Multidisciplinary Sciences
Nicolas Luis Calzetta, Marina Alejandra Gonzalez Besteiro, Vanesa Gottifredi
Article
Biochemistry & Molecular Biology
Michaela Ihle, Stephanie Biber, Insa S. Schroeder, Christine Blattner, Miriam Deniz, Giovanna Damia, Vanesa Gottifredi, Lisa Wiesmueller
Summary: The study reveals distinct DNA replication phenotypes in stem cells and differentiated cells, which are associated with interactions between p53 and POLi proteins. Stem cells slow down DNA replication by promoting complex formation, while differentiated cells synthesize DNA faster, potentially offering therapeutic opportunities focused on DNA replication-based strategies for targeting stem cells.
NUCLEIC ACIDS RESEARCH
(2021)
Review
Oncology
Sebastian Omar Siri, Julieta Martino, Vanesa Gottifredi
Summary: Chromosome instability (CIN) involves increased numerical and structural changes in chromosomes, playing a pivotal role in tumor progression and potential therapeutic targeting. The review delves into the origins of structural CIN, cellular mechanisms, relationships between different CIN phenotypes, and the consequences of structural CIN in cells. The discussion also explores strategies to either prevent or amplify CIN for tumor treatment.
Review
Pharmacology & Pharmacy
Laura Guantay, Cintia Garro, Sebastian Siri, Maria Florencia Pansa, Sonja Ghidelli-Disse, Natalia Paviolo, Ana Racca, Viviana Nicotra, Caius Radu, Jose Luis Bocco, Rosana Felice, Keith H. Jansson, Katja Remlinger, Alejandro Amador, Euan Stronach, Kevin Coleman, Marcel Muelbaier, Gerard Drewes, Isro Gloger, Kevin Madauss, Manuela Garcia, Vanesa Gottifredi, Gaston Soria
Summary: The plant-derived compound Solanocapsine was found to selectively induce Synthetic Lethality (SL) in BRCA2-deficient cells. The nucleotide salvage pathway enzyme deoxycytidine kinase (dCK) was identified as the target responsible for Solanocapsine's SL induction. Inhibition of dCK with the specific inhibitor DI-87 also induced SL in multiple BRCA2-deficient models, highlighting dCK as a promising target for future therapeutic alternatives to PARP inhibitors.
DRUG RESISTANCE UPDATES
(2023)
Article
Biology
Julieta Martino, Sebastian Omar Siri, Nicolas Luis Calzetta, Natalia Soledad Paviolo, Cintia Garro, Maria F. Pansa, Sofia Carbajosa, Aaron C. Brown, Jose Luis Bocco, Israel Gloger, Gerard Drewes, Kevin P. Madauss, Gaston Soria, Vanesa Gottifredi
Summary: Inhibiting ROCK independently triggers synthetic lethality in BRCA2-deficient cells, which is different from the synthetic lethality caused by PARP inhibitors. Cytokinesis failure induces mitotic abnormalities and synthetic lethality in BRCA2-deficient cells.
Article
Multidisciplinary Sciences
Sabrina F. Mansilla, Agostina P. Bertolin, Sofia Venerus Arbilla, Bryan A. Castano, Tiya Jahjah, Jenny K. Singh, Sebastian O. Siri, Maria Victoria Castro, Maria Belen de la Vega, Annabel Quinet, Lisa Wiesmueller, Vanesa Gottifredi
Summary: Recent studies have shown that the choice of a DNA damage tolerance pathway involves competition between PrimPol-mediated repriming and fork reversal. Pol t plays a unique role in regulating this pathway choice, with Pol t deficiency leading to PrimPol-dependent repriming and accelerated DNA replication. However, this excessive participation of PrimPol in DNA elongation can trigger chromosome instability and replication stress signals in Pol t-depleted cells, revealing an unexpected role of Pol t in protecting genome stability.
Article
Biochemistry & Molecular Biology
Stephanie Biber, Helmut Pospiech, Vanesa Gottifredi, Lisa Wiesmuller
NUCLEIC ACIDS RESEARCH
(2020)
Article
Biotechnology & Applied Microbiology
Vanesa Gottifredi
MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS
(2020)
Article
Biochemistry & Molecular Biology
Natalia Soledad Paviolo, Maria Belen de la Vega, Maria Florencia Pansa, Iris Alejandra Garcia, Nicolas Luis Calzetta, Gaston Soria, Vanesa Gottifredi
GENETICS AND MOLECULAR BIOLOGY
(2020)