Article
Cell Biology
Seok-Won Jang, Jung Min Kim
Summary: The Fanconi anemia (FA) DNA repair pathway plays an important role in maintaining genome integrity, as well as in DNA inter-strand crosslink (ICL) repair and stabilizing stalled replication forks. In FA-deficient cells, inhibition of replication protein A (RPA) activates the FA pathway and enhances cellular sensitivity to cisplatin.
Article
Biochemistry & Molecular Biology
Juan A. Cantres-Velez, Justin L. Blaize, David A. Vierra, Rebecca A. Boisvert, Jada L. Garzon, Benjamin Piraino, Winnie Tan, Andrew J. Deans, Niall G. Howlett
Summary: This study identifies a cyclin-dependent kinase (CDK) regulatory phosphosite (S592) proximal to the site of FANCD2 monoubiquitination, the phosphorylation of which affects the function of FANCD2 and mitotic fidelity. Mutation of S592 leads to abrogated monoubiquitination of FANCD2 during the S phase, affecting cell proliferation and mitotic fidelity.
MOLECULAR AND CELLULAR BIOLOGY
(2021)
Article
Cell Biology
Yoko Katsuki, Masako Abe, Seon Young Park, Wenwen Wu, Hiromasa Yabe, Miharu Yabe, Haico van Attikum, Shinichiro Nakada, Tomohiko Ohta, Michael M. Seidman, Yonghwan Kim, Minoru Takata
Summary: RNF168 plays a critical role in recruiting SLX4 to ICL damage sites and is epistatic with SLX4 in promoting MMC tolerance.
Article
Biochemistry & Molecular Biology
Sudipa Mondal, Subba Reddy, Sudit S. Mukhopadhyay
Summary: This study focused on understanding the structure of monoubiquitinated FANCD2 and its interaction with DNA, successfully predicting its structure using a developed method. Docking studies revealed large structural differences between FANCD2 and monoubiquitinated FANCD2.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
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
Biochemistry & Molecular Biology
Simin Zhao, Chengzi Huang, Yajuan Yang, Weiwei Xu, Yongze Yu, Canxin Wen, Lili Cao, Fei Gao, Yingying Qin, Zi-Jiang Chen, Ting Guo, Shidou Zhao
Summary: When DNA interstrand crosslink lesions occur, a core complex of Fanconi anemia proteins promotes the ubiquitination of FANCD2 and FANCI, which recruit downstream factors to repair the lesion. FANCD2 maintains genome stability through both its ubiquitination-dependent and ubiquitination-independent functions. This study analyzed germ cell development in Fancd2 KO and ubiquitination-deficient mutant mice, and found that the ubiquitination-dependent and ubiquitination-independent functions of FANCD2 were required for different aspects of germ cell development.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
Article
Oncology
Jasmine D. Peake, Chiaki Noguchi, Baicheng Lin, Amber Theriault, Margaret O'Connor, Shivani Sheth, Koji Tanaka, Hiroshi Nakagawa, Eishi Noguchi
Summary: The study reveals that acetaldehyde causes DNA damage and impedes replication fork progression, leading to genomic instability in esophageal epithelial cells. FANCD2, which triggers apoptosis upon acetaldehyde exposure and prevents genomic instability in esophageal SCCs, plays a critical role in the replication abnormalities induced by acetaldehyde.
MOLECULAR ONCOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Swarna Beesetti, Shyam Sirasanagandla, Sadie Miki Sakurada, Shondra M. Pruett-Miller, Rhea Sumpter, Beth Levine, Malia B. Potts
Summary: Fanconi anemia is a common inherited bone marrow failure syndrome. FANCL protein is found in mitochondria and its localization is not dependent on its ubiquitin ligase activity. Knockout of FANCL results in increased sensitivity to mitochondrial stress and defective clearing of damaged mitochondria, which can be reversed by reintroduction of wild-type or ubiquitin ligase-deficient FANCL.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2022)
Article
Cell Biology
Shizhi Wang, Bo Ding, Mengjing Cui, Wenjing Yan, Qianqian Xia, Dan Meng, Siyuan Shen, Shuqian Xie, Hua Jin, Xing Zhang
Summary: This study conducted a comprehensive pan-cancer analysis on FARGs, revealing their key roles in HPV-related cancers, especially in cervical cancer. By developing a prognostic risk score model and a nomogram model, accurate predictions were made for overall survival and recurrence-free survival in cervical cancer.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Oncology
Miguel A. Villalona-Calero, John P. Diaz, Wenrui Duan, Zuanel Diaz, Eric D. Schroeder, Santiago Aparo, Troy Gatcliffe, Federico Albrecht, Siddhartha Venkatappa, Victor Guardiola, Sara Garrido, Muni Rubens, Fernando DeZarraga, Hao Vuong
Summary: This study demonstrates the significant antitumor activity of pembrolizumab in malignancies without current FDA approved indications and with functional Fanconi anemia deficiency. The results support further evaluation of FATSI as a discriminatory biomarker for population-selected studies.
BIOMARKER RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Tamara Sijacki, Pablo Alcon, Zhuo A. Chen, Stephen H. McLaughlin, Shabih Shakeel, Juri Rappsilber, Lori A. Passmore
Summary: This study reveals that phosphorylation of FANCI by the ATR DNA damage kinase primes the FANCD2-FANCI clamp for ubiquitination, facilitating the initiation of DNA cross-link repair.
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2022)
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)
Review
Genetics & Heredity
Masamichi Ishiai
Summary: The Fanconi anemia (FA) DNA repair pathway is activated through monoubiquitination of FANCD2 and its binding partner FANCI, regulated by the ATR kinase. This process serves as a good example of ATR's contribution to genome stability.
Review
Biochemistry & Molecular Biology
Winnie Tan, Andrew J. Deans
Summary: The Fanconi Anemia (FA) pathway maintains genome stability by preventing DNA damage, with the FA core complex playing a central role in monoubiquitination of FANCI-FANCD2. Any mutations in the FA core complex can lead to defective monoubiquitination, resulting in various phenotypes including DNA damage sensitivity, birth defects, early-onset bone marrow failure, and cancer.
PROGRESS IN BIOPHYSICS & MOLECULAR BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Emma L. Traband, Sarah R. Hammerlund, Mohammad Shameem, Ananya Narayan, Sanjiv Ramana, Anika Tella, Alexandra Sobeck, Naoko Shima
Summary: This study reports FANCD2-driven MiDAS in untransformed human cells. This form of MiDAS requires a prerequisite step of FANCD2 mono-ubiquitination and primarily acts to preserve CFS stability rather than prevent chromo-some mis-segregation.
JOURNAL OF MOLECULAR BIOLOGY
(2023)
Letter
Biochemical Research Methods
Xin Li, Maurizio Mauro, Zev Williams
Article
Biochemistry & Molecular Biology
Xin Li, Iddo Z. Ben-Dov, Maurizio Mauro, Zev Williams
BMC MOLECULAR BIOLOGY
(2015)
Article
Environmental Sciences
Maurizio Mauro, Fabio Caradonna, Catherine B. Klein
ENVIRONMENTAL AND MOLECULAR MUTAGENESIS
(2016)
Article
Genetics & Heredity
Fabio Caradonna, Maurizio Mauro
Article
Oncology
David A. Vierra, Jada L. Garzon, Meghan A. Rego, Morganne M. Adroved, Maurizio Mauro, Niall G. Howlett
Article
Multidisciplinary Sciences
Angela Lombardi, Jessica Gambardella, Xue-Liang Du, Daniela Sorriento, Maurizio Mauro, Guido Iaccarino, Bruno Trimarco, Gaetano Santulli
SCIENTIFIC REPORTS
(2017)
Article
Environmental Sciences
G. Sciandrello, M. Mauro, I. Catanzaro, M. Saverini, F. Caradonna, G. Barbata
ENVIRONMENTAL AND MOLECULAR MUTAGENESIS
(2011)
Article
Genetics & Heredity
Irene Catanzaro, Fabio Caradonna, Giusi Barbata, Marghereth Saverini, Maurizio Mauro, Giulia Sciandrello
Article
Genetics & Heredity
Maurizio Mauro, Irene Catanzaro, Flores Naselli, Giulia Sciandrello, Fabio Caradonna
Article
Biochemistry & Molecular Biology
Maurizio Mauro, Meghan A. Rego, Rebecca A. Boisvert, Fumiko Esashi, Francesca Cavallo, Maria Jasin, Niall G. Howlett
NUCLEIC ACIDS RESEARCH
(2012)
Article
Biochemistry & Molecular Biology
M. A. Rego, J. A. Harney, M. Mauro, M. Shen, N. G. Howlett
Article
Multidisciplinary Sciences
Rebecca A. Boisvert, Meghan A. Rego, Paul A. Azzinaro, Maurizio Mauro, Niall G. Howlett
Article
Multidisciplinary Sciences
Grasiella Angelina Andriani, Vinnycius Pereira Almeida, Francesca Faggioli, Maurizio Mauro, Wanxia Li Tsai, Laura Santambrogio, Alexander Maslov, Massimo Gadina, Judith Campisi, Jan Vijg, Cristina Montagna
SCIENTIFIC REPORTS
(2016)
Article
Obstetrics & Gynecology
Mario Vega, Maurizio Mauro, Zev Williams
FERTILITY AND STERILITY
(2019)