Article
Biochemistry & Molecular Biology
Hee Jin Chung, Joo Rak Lee, Tae Moon Kim, Soomi Kim, Kibeom Park, Myung-Jin Kim, Eunyoung Jung, Subin Kim, Eun A. Lee, Jae Sun Rae, Sunyoung Hwang, Ja Yil Lee, Orlando D. Scharer, Yonghwan Kim, Kyungjae Myung, Hongtae Kim
Summary: In this study, ZNF212 is identified as a new binding partner for TRAIP and is found to colocalize with sites of DNA damage. Depletion of ZNF212 causes defects in the DDR and HR-mediated repair, and acts upstream of the Neil3 and Fanconi anemia pathways in ICL repair. Furthermore, ZNF212 interacts with NEIL3 and promotes its recruitment to ICL lesions.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Matthew Nolan, Kenneth Knudson, Marina K. Holz, Indrajit Chaudhury
Summary: mTOR interacts and cooperates with FANCD2 during replication stress to provide cellular stability, mediate stalled replication fork restart, and prevent nucleolytic degradation of the nascent DNA strands. This study reveals a novel functional cross-talk between the mTOR and FA DNA repair pathways to ensure genomic stability.
Editorial Material
Cell Biology
Jasmine D. Peake, Kalisse I. Horne, Chiaki Noguchi, John P. Gilligan, Eishi Noguchi
Summary: Alcohol can cause cellular accumulation of acetaldehyde, a major carcinogen, and individuals with deficiency in acetaldehyde detoxification or the Fanconi anemia DNA repair pathway have an increased risk of esophageal squamous-cell carcinoma. This study reveals that acetaldehyde induces DNA damage at the replication fork, leading to replication stress and activation of cell cycle checkpoints. It also demonstrates that the p53 DNA damage response is elevated in response to acetaldehyde and the FA pathway limits genomic instability. These findings highlight the importance of the FA pathway and p53 DNA damage response in protecting against genomic instability and esophageal carcinogenesis.
Review
Biochemistry & Molecular Biology
Daniel R. Semlow, Johannes C. Walter
Summary: This review explores the role of ICLs in DNA repair, the relationship between diseases like Fanconi anemia and cancer with ICL repair, the chemical diversity of ICLs, and how cells unhook these interstrand cross-links. The review also highlights new unhooking strategies, advancements in the structural analysis of the Fanconi anemia pathway, and insights into how cells choose between different ICL repair pathways. Gaps in our understanding of these DNA repair pathways are emphasized throughout the discussion.
ANNUAL REVIEW OF BIOCHEMISTRY, VOL 90, 2021
(2021)
Article
Oncology
Anna Huguet Ninou, Jemina Lehto, Dimitrios Chioureas, Hannah Stigsdotter, Korbinian Schelzig, Emma Akerlund, Greta Gudoityte, Ulrika Joneborg, Joseph Carlson, Jos Jonkers, Brinton Seashore-Ludlow, Nina Marie Susanne Gustafsson
Summary: DNA-damaging chemotherapeutics, such as platinum drugs, rely on the DNA repair capacity of cancer cells for efficacy, but cancer cells often develop resistance by altering their DNA damage response pathways. Targeting PFKFB3, which is commonly overexpressed in cancer, sensitizes cancer cells to platinum drugs and improves treatment efficacy by modulating the Fanconi anemia DNA repair pathway. Inhibition of PFKFB3 disrupts the assembly of key FA repair factors, prevents fork restart, and ultimately leads to an accumulation of DNA damage in replicating cells and fork collapse, enhancing the effectiveness of ICL-inducing cancer treatments.
Article
Environmental Sciences
Yun Zhao, Linqing Wei, Abderrahmane Tagmount, Alex Loguinov, Amin Sobh, Alan Hubbard, Cliona M. McHale, Christopher J. Chang, Chris D. Vulpe, Luoping Zhang
Summary: This study identified genes affecting formaldehyde toxicity in human hematopoietic cells using CRISPR screening, including those that increase sensitivity and resistance, along with related pathways and mechanisms. Results indicated a significant role for formaldehyde metabolism and the Fanconi anemia pathway in toxicity tolerance, and new network analyses revealed potential roles for one-carbon metabolism, fatty acid synthesis, and mTOR signaling in modulating formaldehyde toxicity.
Article
Multidisciplinary Sciences
Yajuan Yang, Weiwei Xu, Fei Gao, Canxin Wen, Simin Zhao, Yongze Yu, Wenlin Jiao, Xin Mi, Yingying Qin, Zi-Jiang Chen, Shidou Zhao
Summary: This study reveals that mouse PGCs experience a high frequency of transcription-replication conflicts, leading to replication stress and DNA damage. The FA pathway is found to play a crucial role in PGC proliferation, and disabling this pathway results in severe cell loss and sterility.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biochemistry & Molecular Biology
Andra Brunner, Qiuzhen Li, Samuele Fisicaro, Alexandros Kourtesakis, Johanna Viiliainen, Henrik J. Johansson, Vijaya Pandey, Adarsh K. Mayank, Janne Lehtio, James A. Wohlschlegel, Charles Spruck, Juha K. Rantala, Lukas M. Orre, Olle Sangfelt
Summary: This study shows that phosphorylation of FANCD2 by CHK1 triggers its degradation via FBXL12, promoting efficient DNA replication under replication stress. Depletion of FBXL12 leads to trapping of FANCD2 on chromatin, causing replication stress and DNA damage. Upregulation of FBXL12 is associated with reduced survival in patients with CYCLIN E-overexpressing breast tumors.
Article
Biochemistry & Molecular Biology
Arun Mouli Kolinjivadi, Haresh Sankar, Ramveer Choudhary, Lavina Sierra Tay, Tuan Zea Tan, Naoko Murata-Kamiya, Dominic Chih-Cheng Voon, Dennis Kappei, Masanori Hatakeyama, Vaidehi Krishnan, Yoshiaki Ito
Summary: The bacterial pathogen H. pylori exploits the host DNA repair proteins to induce genomic instability by downregulating key DNA repair genes such as FANCI, FANCD2, BRCA1, and BRCA2 through the virulence factor CagA. This results in impaired fork stability, increased DNA double strand breaks, and compromised genome stability, revealing a novel mechanism of bacterial virulence.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Sudong Zhan, Jolene Siu, Zhanwei Wang, Herbert Yu, Tedros Bezabeh, Youping Deng, Wei Du, Peiwen Fei
Summary: Fanconi Anemia (FA) is a genetic disease with the largest number of health complications in human organ systems, highlighting the important roles played by FA genes in maintaining human health. The FA signaling network, comprised of FA proteins and other non-FA proteins, is crucial for easing cellular stresses and protecting humans from diseases such as aging and cancer, with the FA D2 group protein (FANCD2) serving as the focal point of FA signaling.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Jessica W. Luzwick, Eszter Dombi, Rebecca A. Boisvert, Sunetra Roy, Soyoung Park, Selvi Kunnimalaiyaan, Steffi Goffart, Detlev Schindler, Katharina Schlacher
Summary: The Fanconi anemia suppressor genes in mitochondria protect mtDNA replication forks, while degradation by MRE11 nuclease leads to loss of nascent mtDNA. Unlike nuclear DNA replication fork stability, mitochondrial replication fork protection does not require pathway activation, revealing a separation between the two stability pathways.
Review
Biochemistry & Molecular Biology
Kazumasa Yoshida, Masatoshi Fujita
Summary: During genome duplication, eukaryotic cells may encounter various replication stresses that can lead to chromosome breaks, genomic instability, and tumor development if not properly resolved. To prevent these consequences, cells have mechanisms in place to enhance the resilience of replication machineries against replication stresses.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2021)
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
Biochemistry & Molecular Biology
Richard O. Adeyemi, Nicholas A. Willis, Andrew E. H. Elia, Connor Clairmont, Shibo Li, Xiaohua Wu, Alan D. D'Andrea, Ralph Scully, Stephen J. Elledge
Summary: Protexin complex, including the REV3 polymerase, establishes a novel fork protection pathway that counteracts fork resection, particularly at ICL stalled forks. This pathway acts independently of BRCA/RAD51-mediated fork stabilization and is crucial for maintaining genomic stability.
Article
Oncology
Jemina Lehto, Anna Huguet Ninou, Dimitrios Chioureas, Jos Jonkers, Nina M. S. Gustafsson
Summary: Chemotherapeutics that introduce DNA crosslinks, like platinum drugs, are used to treat cancers but face limitations due to side effects and acquired resistance. Targeting DNA repair, particularly the interaction between CX3CR1 and the FA repair pathway, holds promise in improving treatment responses and reducing side effects.
Article
Biochemistry & Molecular Biology
Alice Meroni, Giulia Maria Nava, Eliana Bianco, Lavinia Grasso, Elena Galati, Maria Cristina Bosio, Daria Delmastro, Marco Muzi-Falconi, Federico Lazzaro
NUCLEIC ACIDS RESEARCH
(2019)
Article
Cell & Tissue Engineering
Rosalba Monica Ferraro, Gaetana Lanzi, Stefania Masneri, Chiara Barisani, Giovanna Piovani, Giulia Savio, Marco Cattalini, Jessica Galli, Cristina Cereda, Marco Muzi-Falconi, Simona Orcesi, Elisa Fazzi, Silvia Giliani
STEM CELL RESEARCH
(2019)
Article
Biochemistry & Molecular Biology
Diana Zatreanu, Zhong Han, Richard Mitter, Emanuela Tumini, Hannah Williams, Lea Gregersen, A. Barbara Dirac-Svejstrup, Stefania Roma, Aengus Stewart, Andres Aguilera, Jesper Q. Svejstrup
Review
Biochemistry & Molecular Biology
Giulia Maria Nava, Lavinia Grasso, Sarah Sertic, Achille Pellicioli, Marco Muzi Falconi, Federico Lazzaro
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2020)
Article
Cell & Tissue Engineering
Rosalba Monica Ferraro, Stefania Masneri, Gaetana Lanzi, Chiara Barisani, Giovanna Piovani, Giulia Savio, Marco Cattalini, Jessica Galli, Cristina Cereda, Marco Muzi-Falconi, Simona Orcesi, Elisa Fazzi, Silvia Giliani
STEM CELL RESEARCH
(2019)
Article
Cell & Tissue Engineering
Stefania Masneri, Gaetana Lanzi, Rosalba Monica Ferraro, Chiara Barisani, Giovanna Piovani, Giulia Savio, Marco Cattalini, Jessica Galli, Cristina Cereda, Marco Muzi-Falconi, Simona Orcesi, Elisa Fazzi, Silvia Giliani
STEM CELL RESEARCH
(2019)
Article
Cell Biology
Roberto Quadri, Martina Galli, Elena Galati, Giuseppe Rotondo, Guido Roberto Gallo, Davide Panigada, Paolo Plevani, Marco Muzi-Falconi
Review
Genetics & Heredity
Sarah Sertic, Roberto Quadri, Federico Lazzaro, Marco Muzi-Falconi
Article
Cell Biology
Roberto Quadri, Sarah Sertic, Marco Muzi-Falconi
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2020)
Review
Neurosciences
Luca Colnaghi, Diego Rondelli, Marco Muzi-Falconi, Sarah Sertic
Article
Cell Biology
Martina Galli, Laura Diani, Roberto Quadri, Alessandro Nespoli, Elena Galati, Davide Panigada, Paolo Plevani, Marco Muzi-Falconi
Summary: Symmetry breaking by cellular polarization is crucial for the cell-cycle of Saccharomyces cerevisiae cells, allowing bud emergence and growth. The morphogenesis checkpoint coordinates bud formation and cell cycle progression, with the novel role of the kinase haspin in regulating this process. Haspin monitors polarity establishment and links bud emergence to the G2/M cell cycle transition in yeast.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Roberto Quadri, Sarah Sertic, Anna Ghilardi, Diego Rondelli, Guido Roberto Gallo, Luca Del Giacco, Marco Muzi-Falconi
Summary: The study identified an atypical protein kinase, Haspin, as a key regulator of primary cilia dynamics, showing that its activity is essential for the relocation of Dido3-HDAC6 to the basal body, affecting cilia length determination and maintenance. This novel mechanism sheds light on the intricate processes governing primary cilia homeostasis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Elena Galati, Maria C. Bosio, Daniele Novarina, Matteo Chiara, Giulia M. Bernini, Alessandro M. Mozzarelli, Maria L. Garcia-Rubio, Belen Gomez-Gonzalez, Andres Aguilera, Thomas Carzaniga, Marco Todisco, Tommaso Bellini, Giulia M. Nava, Gianmaria Frige, Sarah Sertic, David S. Horner, Anastasia Baryshnikova, Caterina Manzari, Anna M. D'Erchia, Graziano Pesole, Grant W. Brown, Marco Muzi-Falconi, Federico Lazzaro
Summary: This study identifies VID22 as a novel regulator of genome integrity in yeast cells, involved in DNA double-strand break repair and protection of G4-DNA structures. Loss of VID22 leads to increased levels of endogenous DNA damage and hypersensitivity to G4-stabilizing ligands.
NUCLEIC ACIDS RESEARCH
(2021)
Review
Biochemistry & Molecular Biology
Federica Marini, Chetan C. Rawal, Giordano Liberi, Achille Pellicioli
FRONTIERS IN MOLECULAR BIOSCIENCES
(2019)
Meeting Abstract
Dermatology
S. Sertic, D. Rondelli, M. M. Falconi
BRITISH JOURNAL OF DERMATOLOGY
(2019)