Review
Biochemistry & Molecular Biology
Kimon Lemonidis, Connor Arkinson, Martin L. Rennie, Helen Walden
Summary: Fanconi anemia (FA) is a rare genetic disorder caused by mutations in any of the 22 known FA genes, involving the FA pathway for DNA repair and genomic stability maintenance. Ubiquitination and deubiquitination of FANCD2 and FANCI are crucial mechanisms for interstrand cross-link repair.
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)
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
Oncology
Yuqing Li, Yanan Zhang, Qi Yang, Xuantong Zhou, Yuanyuan Guo, Fang Ding, Zhihua Liu, Aiping Luo
Summary: This study investigates the role of FANCI in chemoresistance in ovarian cancer (OVCA). The results show that there are copy number variations (CNVs) in FANCI in OVCA. High expression of FANCI is associated with poor survival and a poor response to chemotherapy in OVCA. Silencing of FANCI inhibits cell migration and invasion and enhances DNA damage-induced apoptosis through the CHK1/2-P53-P21 pathway. These findings suggest that FANCI may be a potential therapeutic target for OVCA patients.
CURRENT CANCER DRUG TARGETS
(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)
Article
Biochemistry & Molecular Biology
Kimon Lemonidis, Martin L. Rennie, Connor Arkinson, Viduth K. Chaugule, Mairi Clarke, James Streetley, Helen Walden
Summary: The monoubiquitination of the FANCI-FANCD2 (ID2) complex plays a crucial role in the repair of DNA interstrand crosslinks. This study presents the cryo-EM structure of the FANCI-ubiquitinated ID2 complex (I(Ub)D2) bound to DNA, showing that the complex adopts a closed conformation and clamps on DNA. The study also reveals that FANCD2 and FANCI have primed lysine residues ready for ubiquitination in the complex. Furthermore, FANCI ubiquitination maintains FANCD2 ubiquitination by preventing excessive deubiquitination and enabling re-ubiquitination within the I(Ub)D2 complex on DNA.
Article
Dentistry, Oral Surgery & Medicine
Michael W. Ho, Mark P. Ryan, Juhi Gupta, Asterios Triantafyllou, Janet M. Risk, Richard J. Shaw, James B. Wilson
Summary: This study aimed to predict malignant transformation (MT) in oral epithelial dysplasia (OED). The results showed that loss of FANCD2 protein expression in patients with OED, combined with higher histologic grade of dysplasia, offered better prediction of MT.
ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY ORAL RADIOLOGY
(2022)
Article
Cell Biology
Robert Goold, Joseph Hamilton, Thomas Menneteau, Michael Flower, Emma L. Bunting, Sarah G. Aldous, Antonio Porro, Jose R. Vicente, Nicholas D. Allen, Hilary Wilkinson, Gillian P. Bates, Alessandro A. Sartori, Konstantinos Thalassinos, Gabriel Balmus, Sarah J. Tabrizi
Summary: The interaction between FAN1 and MLH1 in DNA damage repair pathways plays a crucial role in stabilizing CAG repeats and inhibiting their expansion. FAN1 functions by limiting MLH1 recruitment and promoting accurate repair, suggesting a potential avenue for therapeutic interventions in Huntington's disease.
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
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)
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
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
Oncology
Heidi Kaljunen, Sinja Taavitsainen, Roosa Kaarijarvi, Eerika Takala, Ville Paakinaho, Matti Nykter, G. Steven Bova, Kirsi Ketola
Summary: In this study, it was found that FANCI is an important regulator of the Fanconi anemia pathway in prostate cancer cells. Inactivation of FANCI may convert cancer cells from a resistant state to an eradicable state under the stress of DNA-damaging chemotherapy. Additionally, high expression of FA pathway genes is associated with poorer survival in prostate cancer patients, and genomic alterations of FA pathway members are prevalent in prostate adenocarcinoma patients.
FRONTIERS IN ONCOLOGY
(2023)
Review
Immunology
Karima Landelouci, Shruti Sinha, Genevieve Pepin
Summary: Fanconi Anemia (FA) is a genome instability syndrome caused by mutations in repair genes, leading to congenital abnormalities, premature aging, and bone marrow failure. There is a close relationship between genome instability, inflammation, and the production of type-I Interferon. Understanding the molecular mechanisms of type-I Interferon activation in FA may lead to the discovery of therapeutic targets for the associated inflammation and premature aging.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Article
Cell Biology
Lan Xu, Weiwei Xu, Duan Li, Xiaoxia Yu, Fei Gao, Yingying Qin, Yajuan Yang, Shidou Zhao
Summary: FANCI plays a crucial role in spermatogenesis by regulating DNA repair and maintaining germ cell viability. Deletion of FANCI results in male infertility, abnormal sperm production, and impaired maintenance of undifferentiated spermatogonia in mice. Additionally, FANCI is essential for FANCD2 foci formation and regulation of histone methylation on meiotic sex chromosomes during spermatogenesis.
CELL DEATH & DISEASE
(2021)
Article
Cell Biology
Maya Raghunandan, Indrajit Chaudhury, Stephanie L. Kelich, Helmut Hanenberg, Alexandra Sobeck
Article
Biochemistry & Molecular Biology
Indrajit Chaudhury, Deanna M. Koepp
NUCLEIC ACIDS RESEARCH
(2017)
Review
Genetics & Heredity
Indrajit Chaudhury, Deanna M. Koepp
Article
Biochemistry & Molecular Biology
Nandini Verma, Indrajit Chaudhury, Deepak Kumar, Rakha H. Das
Article
Gastroenterology & Hepatology
Deepak Kumar, Indrajit Chaudhury, Premashis Kar, Rakha H. Das
JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY
(2009)
Article
Biochemistry & Molecular Biology
Indrajit Chaudhury, Daniel R. Stroik, Alexandra Sobeck
MOLECULAR AND CELLULAR BIOLOGY
(2014)
Meeting Abstract
Biochemistry & Molecular Biology
Rakha Hari Das, Nandini Verma, Subhash Kumar Tripathi, Indrajit Chaudhury
NITRIC OXIDE-BIOLOGY AND CHEMISTRY
(2008)
Article
Biochemistry & Molecular Biology
Indrajit Chaudhury, Archana Sareen, Maya Raghunandan, Alexandra Sobeck
NUCLEIC ACIDS RESEARCH
(2013)
Article
Critical Care Medicine
Nandini Verma, Subhash K. Tripathi, Indrajit Chaudhury, Hasi R. Das, Rakha H. Das
Article
Virology
Gourav Mishra, Pooja Chadha, Indrajit Chaudhury, Rakha H. Das
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.
Article
Biochemistry & Molecular Biology
I Chaudhury, SK Raghav, HK Gautam, HR Das, RH Das
Meeting Abstract
Critical Care Medicine
Nandini Verma, Subhash K. Tripathi, Indrajit Chaudhury, Rakha H. Das