Article
Multidisciplinary Sciences
Abdul K. K. Siraj, Rong Bu, Sandeep Kumar Parvathareddy, Kaleem Iqbal, Saud Azam, Zeeshan Qadri, Maha Al-Rasheed, Wael Haqawi, Mark Diaz, Ingrid G. G. Victoria, Ismail A. A. Al-Badawi, Asma Tulbah, Fouad Al-Dayel, Dahish Ajarim, Khawla S. S. Al-Kuraya
Summary: By screening 918 breast cancer/ovarian cancer patients from Saudi Arabia, we identified six cases with pathogenic/likely pathogenic variants in the PALB2 gene, accounting for 0.65% of the entire cohort. Among these cases, two carried pathogenic variants and four carried likely pathogenic variants. All affected carriers had breast cancer, with a median age of diagnosis at 39.5 years, and only two cases had a documented family history of cancer.
SCIENTIFIC REPORTS
(2023)
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
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
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
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
Violeta Serra, Anderson T. Wang, Marta Castroviejo-Bermejo, Urszula M. Polanska, Marta Palafox, Andrea Herencia-Ropero, Gemma N. Jones, Zhongwu Lai, Joshua Armenia, Filippos Michopoulos, Alba Llop-Guevara, Rachel Brough, Aditi Gulati, Stephen J. Pettitt, Krishna C. Bulusu, Jenni Nikkila, Zena Wilson, Adina Hughes, Paul W. G. Wijnhoven, Ambar Ahmed, Alejandra Bruna, Albert Gris-Oliver, Marta Guzman, Olga Rodriguez, Judit Grueso, Joaquin Arribas, Javier Cortes, Cristina Saura, Alan Lau, Susan Critchlow, Brian Dougherty, Carlos Caldas, Gordon B. Mills, J. Carl Barrett, Josep V. Forment, Elaine Cadogan, Christopher J. Lord, Cristina Cruz, Judith Balmana, Mark J. O'Connor
Summary: Targeting the replication stress response is a valid therapeutic option to overcome PARPi resistance, providing new strategies for treating tumors such as breast and ovarian cancer.
CLINICAL CANCER RESEARCH
(2022)
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
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.
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
Mika Iwai, Taisuke Kajino, Masahiro Nakatochi, Kiyoshi Yanagisawa, Yasuyuki Hosono, Hisanori Isomura, Yukako Shimada, Motoshi Suzuki, Ayumu Taguchi, Takashi Takahashi
Summary: In this study, a novel lncRNA called TILR was identified as a constitutive negative regulator of p53 expression, playing a role in the development of lung cancer. It was found that TILR interacts with the protein PCBP2 and binds to p53 mRNA, leading to the suppression of p53 expression and activation of downstream genes involved in apoptosis. Furthermore, TILR was shown to be involved in a positive feedback loop with p53 and Fanconi anemia pathway genes. These findings highlight the importance of TILR in regulating p53 expression and apoptosis in lung cancer.
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
Savannah J. Weeks-Pollenz, Yasmin Ali, Leslie A. Morris, Vincent A. Sutera, Elizabeth E. Dudenhausen, Margaret Hibnick, Susan T. Lovett, Linda B. Bloom
Summary: Escherichia coli YoaA, in conjunction with chi, aids in resolving DNA damage during DNA synthesis. YoaA and chi form a separate complex from DNA polymerase III. The YoaA-chi complex exhibits DNA-dependent ATPase activity and can unwind forked duplex DNA with 3' and 5' single-stranded overhangs. Additionally, YoaA-chi can unwind damaged DNA with abasic sites or damage at the 3' ends. These findings provide biochemical evidence that YoaA is an iron-sulfur helicase and suggest that YoaA-chi is the physiologically relevant form of the helicase.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
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
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)
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.
Article
Biochemistry & Molecular Biology
Muzammil Ahmad, Yutong Xue, Seung Kyu Lee, Jennifer L. Martindale, Weiping Shen, Wen Li, Sige Zou, Maria Ciaramella, Helene Debat, Marc Nadal, Fenfei Leng, Hongliang Zhang, Quan Wang, Grace Ee-Lu Siaw, Hengyao Niu, Yves Pommier, Myriam Gorospe, Tao-Shih Hsieh, Yuk-Ching Tse-Dinh, Dongyi Xu, Weidong Wang
NUCLEIC ACIDS RESEARCH
(2016)
Article
Biochemistry & Molecular Biology
Muzammil Ahmad, Weiping Shen, Wen Li, Yutong Xue, Sige Zou, Dongyi Xu, Weidong Wang
NUCLEIC ACIDS RESEARCH
(2017)
Article
Biochemistry & Molecular Biology
Florian Rohleder, Jing Huang, Yutong Xue, Jochen Kuper, Adam Round, Michael Seidman, Weidong Wang, Caroline Kisker
NUCLEIC ACIDS RESEARCH
(2016)
Article
Cell Biology
Chen Ling, Jing Huang, Zhijiang Yan, Yongjiang Li, Mioko Ohzeki, Masamichi Ishiai, Dongyi Xu, Minoru Takata, Michael Seidman, Weidong Wang
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Chemistry, Medicinal
Nihar Ranjan, Sandra Story, Geraldine Fulcrand, Fenfei Leng, Muzammil Ahmad, Ada King, Souvik Sur, Weidong Wang, Yuk-Ching Tse-Dinh, Dev P. Arya
JOURNAL OF MEDICINAL CHEMISTRY
(2017)
Article
Biochemistry & Molecular Biology
Muzammil Ahmad, Dongyi Xu, Weidong Wang
Article
Oncology
Jiyoung Kim, Ji Heon Noh, Seung-Kyu Lee, Rachel Munk, Alexei Sharov, Elin Lehrmann, Yongqing Zhang, Weidong Wang, Kotb Abdelmohsen, Myriam Gorospe
Article
Multidisciplinary Sciences
Jian Sima, Zhijiang Yan, Yaohui Chen, Elin Lehrmann, Yongqing Zhang, Ramaiah Nagaraja, Weidong Wang, Zhong Wang, David Schlessinger
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2018)
Article
Multidisciplinary Sciences
Seung Kyu Lee, Yutong Xue, Weiping Shen, Yongqing Zhang, Yuyoung Joo, Muzammil Ahmad, Madoka Chinen, Yi Ding, Wai Lim Ku, Supriyo De, Elin Lehrmann, Kevin G. Becker, Elissa P. Lei, Keji Zhao, Sige Zou, Alexei Sharov, Weidong Wang
NATURE COMMUNICATIONS
(2018)
Article
Cell Biology
Jing Huang, Jing Zhang, Marina A. Bellani, Durga Pokharel, Julia Gichimu, Ryan C. James, Himabindu Gali, Chen Ling, Zhijiang Yan, Dongyi Xu, Junjie Chen, Amom Ruhikanta Meetei, Lei Li, Weidong Wang, Michael M. Seidman
Review
Genetics & Heredity
Seung Kyu Lee, Weidong Wang
Article
Multidisciplinary Sciences
Yuyoung Joo, Yutong Xue, Yue Wang, Ross A. McDevitt, Nirnath Sah, Simone Bossi, Shuaikun Su, Seung Kyu Lee, Wei Peng, Aoji Xie, Yongqing Zhang, Yi Ding, Wai Lim Ku, Soumita Ghosh, Kenneth Fishbein, Weiping Shen, Richard Spencer, Kevin Becker, Keji Zhao, Mark P. Mattson, Henriette van Praag, Alexei Sharov, Weidong Wang
NATURE COMMUNICATIONS
(2020)
Article
Multidisciplinary Sciences
Young-Kwon Park, Ji-Eun Lee, Zhijiang Yan, Kaitlin McKernan, Tommy O'Haren, Weidong Wang, Weiqun Peng, Kai Ge
Summary: The study reveals that BAF and MLL4 are interdependent in promoting enhancer activation by lineage-determining transcription factors during adipogenesis, providing a positive feedback mechanism for the activation of cell type-specific enhancers.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Shuaikun Su, Yutong Xue, Seung Kyu Lee, Yongqing Zhang, Jinshui Fan, Supriyo De, Alexei Sharov, Weidong Wang
Summary: In response to starvation, the complex of topoisomerase 3b (TOP3B) and TDRD3 can enhance both transcriptional activation and repression, similar to other topoisomerases. The genes enhanced by TOP3B-TDRD3 are long and highly-expressed, and are preferentially stimulated by other topoisomerases as well. Inactivation of TOP3B, TDRD3, or TOP3B topoisomerase activity disrupts transcription of both starvation-activated genes (SAGs) and starvation-repressed genes (SRGs). Additionally, TOP3B-TDRD3 and elongating RNAPII display increased binding to TOP3B-dependent SAGs in response to starvation.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Tianyi Zhang, Yutong Xue, Shuaikun Su, Valerie Altouma, Katherine Ho, Jennifer L. Martindale, Seung-Kyu Lee, Weiping Shen, Aaron Park, Yongqing Zhang, Supriyo De, Myriam Gorospe, Weidong Wang
Summary: Nocte, an RNA-binding protein, plays a crucial role in Drosophila eye development by enhancing translation of mRNAs with long uORFs, particularly glass mRNA. Nocte interacts with translation factors eIF3 and Rack1 through its BAT2 domain to counteract translational suppression caused by long uORFs. Disruption of Nocte function can lead to developmental defects and neurological disorders.
NUCLEIC ACIDS RESEARCH
(2023)