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
Medicine, Research & Experimental
Wei Wei, Fangfang Shi, Yang Xu, Yang Jiao, Ying Zhang, Qiuxiang Ou, Xue Wu, Lingyi Yang, Jinhuo Lai
Summary: Next-generation sequencing was used to investigate molecular features in NSCLC patients with pathogenic/likely pathogenic ATM/ATR mutations. The results were validated using an external cohort of NSCLC patients.
JOURNAL OF TRANSLATIONAL MEDICINE
(2023)
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.
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
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
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
Esther Cabanas Morafraile, Javier Perez-Pena, Jesus Fuentes-Antras, Aranzazu Manzano, Pedro Perez-Segura, Atanasio Pandiella, Eva M. Galan-Moya, Alberto Ocana
Summary: Breast cancer is the most common invasive tumor in women and identification of druggable targets to improve current therapies is a major goal. In this study, an in silico analysis of transcriptomic datasets in breast cancer revealed upregulated genes involved in DNA damage response pathways like ATM/ATR, BARD1, and Fanconi Anemia, which correlated with worse prognosis. Understanding these genetic vulnerabilities may help in developing improved therapeutic strategies for breast cancer.
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
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
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)
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)
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
Biochemistry & Molecular Biology
Arvind Panday, Nicholas A. Willis, Rajula Elango, Francesca Menghi, Erin E. Duffey, Edison T. Liu, Ralph Scully
Summary: The study reveals that the FANCM gene encodes a multi-domain scaffolding and motor protein that regulates repair pathway choice at stalled replication forks, and its ATPase function may be a promising target for therapy of BRCA1-linked cancer.
Article
Genetics & Heredity
Lily Chien Wang, Stacie Stone, Maureen Elizabeth Hoatlin, Jean Gautier
Article
Oncology
Igor Landais, Alexandra Sobeck, Stacie Stone, Alexis LaChapelle, Maurcen E. Hoatlin
INTERNATIONAL JOURNAL OF CANCER
(2009)
Article
Biochemistry & Molecular Biology
Zhijiang Yan, Mathieu Delannoy, Chen Ling, Danielle Daee, Fekret Osman, Parameswary A. Muniandy, Xi Shen, Anneke B. Oostra, Hansen Du, Jurgen Steltenpool, Ti Lin, Beatrice Schuster, Chantal Decaillet, Andrzej Stasiak, Alicja Z. Stasiak, Stacie Stone, Maureen E. Hoatlin, Detlev Schindler, Christopher L. Woodcock, Hans Joenje, Ranjan Sen, Johan P. de Winter, Lei Li, Michael M. Seidman, Matthew C. Whitby, Kyungjae Myung, Angelos Constantinou, Weidong Wang
Review
Oncology
Stacie Ittershagen, Solveig Ericson, Lamis Eldjerou, Ali Shojaee, Eric Bleickardt, Manisha Patel, Tetiana Taran, Oezlem Anak, Charlene Hall, Mimi Leung, Deborah Roccoberton, Florence Salmon, Miriam Fuchs, Vadim Romanov, David Lebwohl
CURRENT HEMATOLOGIC MALIGNANCY REPORTS
(2019)
Article
Biochemistry & Molecular Biology
Maya Raghunandan, Jung Eun Yeo, Ryan Walter, Kai Saito, Adam J. Harvey, Stacie Ittershagen, Eun-A Lee, Jihyeon Yang, Maureen E. Hoatlin, Anja K. Bielinsky, Eric A. Hendrickson, Orlando Scharer, Alexandra Sobeck
HUMAN MOLECULAR GENETICS
(2020)
Article
Medicine, Research & Experimental
Gentry King, Stacie Ittershagen, Luyang He, Ying Shen, Frank Li, Reginald Villacorta
Summary: This study described real-world treatment patterns and outcomes for patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) in the USA. The study found that most patients received first-line treatment in accordance with clinical practice guidelines, but overall survival remained poor. The study highlights the need for novel therapies to improve patient survival.
ADVANCES IN THERAPY
(2022)
Article
Cell Biology
Stacie Stone, Alexandra Sobeck, Margriet van Kogelenberg, Bendert de Graaf, Hans Joenje, Jan Christian, Maureen E. Hoatlin
Article
Biochemistry & Molecular Biology
A. Sobeck, S. Stone, M. E. Hoatlin
MOLECULAR AND CELLULAR BIOLOGY
(2007)
Article
Genetics & Heredity
AR Meetei, AL Medhurst, C Ling, YT Xue, TR Singh, P Bier, J Steltenpool, S Stone, I Dokal, CG Mathew, M Hoatlin, H Joenje, JP de Winter, WD Wang
Article
Biochemistry & Molecular Biology
MS Dai, N Chevallier, S Stone, MC Heinrich, M McConnell, T Reuter, HE Broxmeyer, JD Licht, L Lu, ME Hoatlin
JOURNAL OF BIOLOGICAL CHEMISTRY
(2002)
Article
Biochemistry & Molecular Biology
JP de Winter, L van der Weel, J de Groot, S Stone, Q Waisfisz, F Arwert, RJ Scheper, FAE Kruyt, ME Hoatlin, H Joenje
HUMAN MOLECULAR GENETICS
(2000)
Article
Hematology
MC Heinrich, KV Silvey, S Stone, AJ Zigler, DJ Griffith, M Montalto, L Chai, Y Zhi, ME Hoatlin
Review
Biochemistry & Molecular Biology
A Sobeck, S Stone, V Costanzo, B de Graaf, T Reuter, J de Winter, M Wallisch, Y Akkari, S Olson, WD Wang, H Joenje, JL Christian, PJ Lupardus, KA Cimprich, J Gautier, ME Hoatlin
MOLECULAR AND CELLULAR BIOLOGY
(2006)
Article
Cell Biology
HJ van de Vrugt, M Koomen, MAD Berns, Y de Vries, MA Rooimans, L van der Weel, E Blom, J de Groot, RJ Schepers, S Stone, ME Hoatlin, NC Cheng, H Joenje, F Arwert