Article
Multidisciplinary Sciences
Carla Umansky, Agustin E. Morellato, Matthias Rieckher, Marco A. Scheidegger, Manuela R. Martinefski, Gabriela A. Fernandez, Oleg Pak, Ksenia Kolesnikova, Hernan Reingruber, Mariela Bollini, Gerry P. Crossan, Natascha Sommer, Maria Eugenia Monge, Bjorn Schumacher, Lucas B. Pontel
Summary: Formaldehyde (FA) not only exerts cytotoxicity through DNA damage, but also triggers cellular redox imbalance by reacting with glutathione (GSH). GSH synthesis and the enzyme alcohol dehydrogenase 5 (ADH5) play crucial roles in preventing FA cytotoxicity. These findings are important for patients with mutations in FA detoxification systems and suggest potential therapeutic benefits of thiol-rich antioxidants.
NATURE COMMUNICATIONS
(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
Longhao Wang, Tao Hu, Zhibo Shen, Yuanyuan Zheng, Qishun Geng, Lifeng Li, Beibei Sha, Miaomiao Li, Yaxin Sun, Yongjun Guo, Wenhua Xue, Dan Xuan, Ping Chen, Jie Zhao
Summary: The study revealed that targeting the deubiquitinating enzyme USP1 may be a potential strategy for the treatment of hepatocellular carcinoma (HCC). The USP1 inhibitor ML-323 inhibited the growth of HCC cells and induced cell cycle arrest. ML-323 treatment resulted in the accumulation of ubiquitinated proteins, induction of endoplasmic reticulum stress, and Noxa-dependent apoptosis. Additionally, active endoplasmic reticulum stress induced protective autophagy through AMPK phosphorylation.
CELL DEATH & DISEASE
(2022)
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
Genetics & Heredity
Lisa J. McReynolds, Neelam Giri, Lisa Leathwood, Maureen O. Risch, Ann G. Carr, Blanche P. Alter
Summary: The risk of cancer is not increased in individuals with single pathogenic FA gene variant, according to a study on relatives of patients with FA. This finding is crucial for counseling and managing individuals with FA variants.
GENETICS IN MEDICINE
(2022)
Article
Pediatrics
Tomasz Jarmolinski, Monika Rosa, Blanka Rybka, Renata Ryczan-Krawczyk, Kornelia Gajek, Katarzyna Bogunia-Kubik, Maja Klaudel-Dreszler, Piotr Czubkowski, Piotr Kalicinski, Joanna Teisseyre, Marek Stefanowicz, Ewa Gorczynska, Krzysztof Kalwak, Marek Ussowicz
Summary: A child with Fanconi anemia underwent orthotopic liver transplantation (OLT) after hematopoietic stem cell transplantation (HSCT) complicated by acute graft versus host disease (GVHD). The liver can serve as a clinically significant source of hematopoietic stem cells. Close monitoring of hematopoietic chimerism after OLT is necessary in patients at risk for complications such as GVHD.
FRONTIERS IN PEDIATRICS
(2022)
Article
Chemistry, Multidisciplinary
Sally B. Morton, L. David Finger, Roxanne van der Sluijs, William D. Mulcrone, Michael Hodskinson, Christopher L. Millington, Christina Vanhinsbergh, Ketan J. Patel, Mark J. Dickman, Puck Knipscheer, Jane A. Grasby, David M. Williams
Summary: DNA interstrand cross-links (ICLs) have significant implications for DNA replication and transcription, and understanding their repair is crucial. This study presents an efficient method for generating reduced acetaldehyde ICLs, which can be used to study their recognition and repair. The methodology described here shows promising results and will facilitate further research in cross-link repair.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Chemistry, Multidisciplinary
David M. Williams, Sally B. Morton, L. David Finger, Roxanne van der Sluijs, William D. Mulcrone, Michael Hodskinson, Christopher L. Millington, Christina Vanhinsbergh, Ketan J. Patel, Mark J. Dickman, Puck Knipscheer, Jane A. Grasby
Summary: DNA cross-link (ICLs) can cause lethal events such as cancer or bone marrow failure during replication and transcription. The Fanconi Anemia (FA) pathway proteins are responsible for repairing ICLs, but the details of the pathway are not fully known. Methods to create DNA containing ICLs are crucial for further understanding cross-link repair. A major method to form ICLs in vivo is through DNA reaction with acetaldehyde from ethanol metabolism. This research presents an efficient approach using a novel N2-((R)-4-trifluoroacetamidobutan-2-yl)-2'-deoxyguanosine phosphoramidite for preparing reduced acetaldehyde ICLs. The simplicity, efficiency, and stability of this method will contribute to future studies on cross-link repair.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Oncology
Daijing Nie, Jing Zhang, Fang Wang, Xvxin Li, Lili Liu, Wei Zhang, Panxiang Cao, Xue Chen, Yang Zhang, Jiaqi Chen, Xiaoli Ma, Xiaosu Zhou, Qisheng Wu, Ming Liu, Mingyue Liu, Wenjun Tian, Hongxing Liu
Summary: The study suggests that heterozygous mutations in Fanconi anemia genes can contribute to hematologic disorders, particularly aplastic anemia and leukemia. Different genes have varying frequencies of mutations, with some genes showing associations with specific subgroups of hematologic malignancies.
FRONTIERS OF MEDICINE
(2022)
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
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
Medical Laboratory Technology
Lixian Chang, Li Zhang, Wenbin An, Yang Wan, Yuli Cai, Yang Lan, Aoli Zhang, Lipeng Liu, Min Ruan, Xiaoming Liu, Ye Guo, Wenyu Yang, Xiaojuan Chen, Yumei Chen, Shuchun Wang, Yao Zou, Weiping Yuan, Xiaofan Zhu
Summary: A study investigated the clinical features and genotype/phenotype correlation of 148 Chinese pediatric Fanconi anemia (FA) patients. FA-A was the most common subtype in the cohort, and finger and skin deformities were the most frequent malformations. New mutation sites and their association with prognosis were identified, and chromosome abnormalities were found to be closely linked to the progression of FA to leukemia.
CLINICA CHIMICA ACTA
(2023)
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
Ilaria Laudadio, Alex Bastianelli, Valerio Fulci, Claudia Carissimi, Eleonora Colantoni, Francesca Palone, Roberta Vitali, Elisa Lorefice, Salvatore Cucchiara, Anna Negroni, Laura Stronati
Summary: This study investigated the role of ZNF281 in intestinal fibrosis, revealing its significant involvement in fibrogenesis by controlling gene expression that affects fibroblast activation and differentiation into myofibroblasts.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Medicine, Research & Experimental
Xinbo Zhang, Jonathan Sun, Alberto Canfran-Duque, Binod Aryal, George Tellides, Ying Ju Chang, Yajaira Suarez, Timothy F. Osborne, Carlos Fernandez-Hernando
Summary: Epigenetic modifications, particularly SETDB2, play a crucial role in regulating immune response during atherosclerosis. Upregulation of SETDB2 is associated with proinflammatory macrophages, while its deficiency exacerbates vascular inflammation. Loss of SETDB2 affects monocyte population and gene expression related to inflammation in atherosclerotic plaques.
Article
Oncology
Eunice Fabian-Morales, David Vallejo-Escamilla, Adriana Gudino, Alfredo Rodriguez, Rodrigo Gonzalez-Barrios, Yameli L. Rodriguez Torres, Clementina Castro Hernandez, Alfredo H. Torre-Lujan, Diego A. Oliva-Rico, Erandhi C. Ornelas Guzman, Alejandro Lopez Saavedra, Sara Frias, Luis A. Herrera
Summary: Resistance to TKI in CML is correlated with high levels of structural disruption of CT9 and CT22 in CD34+ cells, increased CT volumes (especially for CT22), intermingling between CT9 and CT22, and an open-chromatin epigenetic mark in CT22. These findings could potentially serve as a prognostic marker of response to treatment in CML and provide insights into mechanisms of TKI resistance.
INTERNATIONAL JOURNAL OF CANCER
(2022)
Article
Biochemistry & Molecular Biology
Pedro Reyes, Benilde Garcia-de Teresa, Ulises Juarez, Fernando Perez-Villatoro, Moises O. Fiesco-Roa, Alfredo Rodriguez, Bertha Molina, Maria Teresa Villarreal-Molina, Jorge Melendez-Zajgla, Alessandra Carnevale, Leda Torres, Sara Frias
Summary: This study evaluated the characteristics of a novel founder FANCG PV found in three Fanconi anemia patients from the Mixe community of Oaxaca, Mexico. The patients showed chromosomal instability and a homozygous PV, and their phenotype varied in severity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Gastroenterology & Hepatology
Takeshi Katsuda, Hector Cure, Jonathan Sussman, Kamen P. Simeonov, Christopher Krapp, Zoltan Arany, Markus Grompe, Ben Z. Stanger
Summary: This study introduces a rapid in vivo multiplexed editing (RIME) method that enables the efficient inactivation of one or more genes in the mouse liver. The method is quick, efficient, and cost-effective, making it a valuable tool for analyzing multiple genes in vivo.
Review
Oncology
Moises O. Fiesco-Roa, Benilde Garcia-de Teresa, Paula Leal-Anaya, Renee van 't Hek, Talia Wegman-Ostrosky, Sara Frias, Alfredo Rodriguez
Summary: Inherited bone marrow failure syndromes are a group of complex genetic diseases associated with disrupted genome maintenance, leading to a variety of clinical manifestations. These diseases require high index of suspicion and should be considered even in the absence of obvious clinical manifestations.
FRONTIERS IN ONCOLOGY
(2022)
Article
Multidisciplinary Sciences
Netanel Loyfer, Judith Magenheim, Ayelet Peretz, Gordon Cann, Joerg Bredno, Agnes Klochendler, Ilana Fox-Fisher, Sapir Shabi-Porat, Merav Hecht, Tsuria Pelet, Joshua Moss, Zeina Drawshy, Hamed Amini, Patriss Moradi, Sudharani Nagaraju, Dvora Bauman, David Shveiky, Shay Porat, Uri Dior, Gurion Rivkin, Omer Or, Nir Hirshoren, Einat Carmon, Alon Pikarsky, Abed Khalaileh, Gideon Zamir, Ronit Grinbaum, Machmud Abu Gazala, Ido Mizrahi, Noam Shussman, Amit Korach, Ori Wald, Uzi Izhar, Eldad Erez, Vladimir Yutkin, Yaacov Samet, Devorah Rotnemer Golinkin, Kirsty L. Spalding, Henrik Druid, Peter Arner, A. M. James Shapiro, Markus Grompe, Alex Aravanis, Oliver Venn, Arash Jamshidi, Ruth Shemer, Yuval Dor, Benjamin Glaser, Tommy Kaplan
Summary: DNA methylation is an important epigenetic mark that regulates gene expression and chromatin organization. This study presents a human methylome atlas based on deep whole-genome bisulfite sequencing, providing a comprehensive analysis of 39 cell types from 205 healthy tissue samples. The atlas reveals tissue-specific methylation patterns and potential biomarkers for liquid biopsies.
Article
Genetics & Heredity
Alfredo Rodriguez, Michael Epperly, Jessica Filiatrault, Martha Velazquez, Chunyu Yang, Kelsey McQueen, Larissa A. Sambel, Huy Nguyen, Divya Ramalingam Iyer, Ulises Juarez, Cecilia Ayala-Zambrano, David B. Martignetti, Sara Frias, Renee Fisher, Kalindi Parmar, Joel S. Greenberger, Alan D. D'Andrea
Summary: Overexpression of the TGF beta pathway impairs the proliferation of hematopoietic stem and progenitor cells in Fanconi anemia. Genetic disruption of Smad3, a transducer of the canonical TGF beta pathway, modifies the phenotype of Fancd2-deficient mouse models, leading to high levels of embryonic lethality. The activation of the non-canonical TGF beta-ERK pathway is critical for the survival of Fancd2-Smad3 double knockout mice, but it also results in enhanced genomic instability and ineffective hematopoiesis.
Article
Biology
Cecilia Ayala-Zambrano, Mariana Yuste, Sara Frias, Benilde Garcia-de-Teresa, Luis Mendoza, Eugenio Azpeitia, Alfredo Rodriguez, Leda Torres
Summary: Double strand break (DSB) repair is crucial for maintaining genome integrity and deficiency in DSB repair can lead to various pathologies. There are different pathways involved in DSB repair, including homologous recombination (HR), non-homologous end joining (NHEJ), microhomology-mediated end-joining (MMEJ), and single-strand annealing (SSA). Epigenetic modifications of histones also play a role in regulating the choice of DSB repair pathway. A Boolean network model was developed to simulate and predict the response of DSB repair pathways, and experimental validation confirmed the predictions.
JOURNAL OF THEORETICAL BIOLOGY
(2023)
Meeting Abstract
Oncology
Liya Ding, Qiwei Wang, Antons Martincuks, Michael Kearns, Tao Jiang, Ziying Lin, Xin Cheng, Changli Qian, Hye-Jung Kim, Inga-Maria Launonen, Anniina Farkkila, Thomas Roberts, Joyce Liu, Panagiotis Konstantinopoulos, Ursula Matulonis, Hua Yu, Jean Zhao
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Meeting Abstract
Environmental Sciences
Liisa Kauppi, Sanna Pikkusaari, Manuela Tumiati, Anni Virtanen, Taru Muranen, Jaana Oikkonen, Yilin Li, Sampsa Hautaniemi, Fernando Perez, Anniina Farkkila, Johanna Hynninen, Sakari Hietanen, Olli Carpen
ENVIRONMENTAL AND MOLECULAR MUTAGENESIS
(2022)
Article
Pediatrics
Moises O. Fiesco-Roa, Paulina G. Gomez-Moreno, Rubi M. Espinosa-Curiel, Alfredo Rodriguez, Sara Frias
ACTA PEDIATRICA DE MEXICO
(2022)
Article
Pediatrics
Bertha Molina, Sandra Ramos, Sara Frias
Summary: Fanconi anemia is a rare disease that requires accurate diagnosis for appropriate management and counseling. The gold standard for diagnosis is the chromosomal aberration test, which can be performed in various tissues. Diagnosis and chromosome analysis require tightly controlled interpretation by highly specialized personnel.
ACTA PEDIATRICA DE MEXICO
(2022)
