Article
Biochemistry & Molecular Biology
Yongze Yu, Weiwei Xu, Canxin Wen, Simin Zhao, Guangyu Li, Ran Liu, Zi-Jiang Chen, Yingying Qin, Jinlong Ma, Yajuan Yang, Shidou Zhao
Summary: In this study, Ube2t knockout mice showed defects in the proliferation of primordial germ cells (PGCs), resulting in severe loss of germ cells after birth. Deletion of UBE2T exacerbated DNA damage and activated the p53 pathway. The study also revealed that UBE2T resolves transcription-replication conflicts, protects common fragile sites, and promotes mitotic DNA synthesis to maintain the genomic stability of PGCs. Overall, these findings provide new insights into the function and regulatory mechanisms of the Fanconi anemia pathway in ensuring the normal development of PGCs.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2023)
Article
Multidisciplinary Sciences
Shyam Twayana, Albino Bacolla, Angelica Barreto-Galvez, Ruth B. De-Paula, William C. Drosopoulos, Settapong T. Kosiyatrakul, Eric E. Bouhassira, John A. Tainer, Advaitha Madireddy, Carl L. Schildkraut
Summary: The study reveals the crucial role of Pol eta in the replication of common fragile sites (CFSs), highlighting how its deficiency can lead to replication pausing and genetic variations. Presence of non-B DNA structures may increase replication hindrance. Activity of Pol eta in replicating through CFSs may result in genetic variations found in the human population at these sites.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(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.
Review
Genetics & Heredity
Rachel Adihe Lokanga, Daman Kumari, Karen Usdin
Summary: The human genome contains fragile chromosomal regions that demonstrate breaks, gaps, or constrictions under replication stress. Common fragile sites are induced by aphidicolin, while rare fragile sites are induced by folate stress. Different fragile sites have distinct molecular bases and can cause chromosomal abnormalities, some of which are associated with intellectual disabilities.
FRONTIERS IN GENETICS
(2021)
Review
Biology
Benjamin S. Simpson, Hayley Pye, Hayley C. Whitaker
Summary: Recent developments in sequencing the cancer genome have identified 16 signatures of structural variants across 38 tumour types, with some of the variants occurring at fragile sites like NAALADL2. These copy-number variations at fragile sites may have a significant impact on cell signalling.
COMMUNICATIONS BIOLOGY
(2021)
Review
Genetics & Heredity
Fang Ji, Xinli Zhu, Hongwei Liao, Liujian Ouyang, Yingfei Huang, Madiha Zahra Syeda, Songmin Ying
Summary: This review provides an update on the research progress of common fragile sites (CFSs), including mapping and sequencing techniques, as well as hypotheses on the fragility origin of CFSs. By analyzing the locations, sequences, and replication/transcription of CFSs, this review presents the latest research status of CFSs and potentially offers a new framework for future CFS research.
FRONTIERS IN GENETICS
(2022)
Article
Multidisciplinary Sciences
Franklin Mayca Pozo, Xinran Geng, Ilaria Tamagno, Mark W. Jackson, Ernest G. Heimsath, John A. Hammer, Richard E. Cheney, Youwei Zhang
Summary: MYO10 overexpression in tumors increases genomic instability, induces an inflammatory response, and accelerates tumor growth, while depletion of MYO10 reduces genomic instability and inflammation signaling, slowing down tumor progression. MYO10 promotes tumor progression by inducing genomic instability, which creates an immunogenic environment for immune checkpoint blockades.
Article
Biology
Philippe Fernandes, Benoit Miotto, Claude Saint-Ruf, Maha Said, Viviana Barra, Viola Nahse, Silvia Ravera, Enrico Cappelli, Valeria Naim
Summary: FANCD2 regulates CFS stability by dampening mitochondrial stress response and preventing mitochondrial dysfunction; activation of mitochondrial stress signaling induces CFS gene expression, with FANCD2 mediating inhibition of CFS gene transcription and promotion of stability.
COMMUNICATIONS BIOLOGY
(2021)
Article
Agriculture, Dairy & Animal Science
Marta Kuchta-Gladysz, Ewa Wojcik, Anna Grzesiakowska, Katarzyna Rymuza, Olga Szeleszczuk
Summary: The paper explores the karyotypes of blue and silver foxes, as well as their hybrids, focusing on A and B chromosome numbers and fragile site frequencies. Genome stability is influenced by Robertsonian translocations in blue foxes and B chromosomes in silver foxes. The study uses fragile sites assay as a biomarker to evaluate genome stability in foxes, with a lower frequency of instabilities observed in healthy individuals. The assay can assist in selecting individuals with stable genomes for breeding, particularly for the conservation of endangered species like the blue fox.
Article
Multidisciplinary Sciences
Anna Kychygina, Marina Dall'Osto, Joshua A. M. Allen, Jean-Charles Cadoret, Vincent Piras, Hilda A. Pickett, Laure Crabbe
Summary: The study reveals that defects in the nuclear lamina in HGPS cells lead to changes in telomere organization and chromatin state, affecting replication timing and DNA synthesis process. Increasing dNTP levels in HGPS cells can rescue fragile telomeres and enhance replicative capacity, highlighting a functional connection between NE dysfunction and telomere homeostasis in the context of premature aging.
SCIENTIFIC REPORTS
(2021)
Article
Multidisciplinary Sciences
Aleksandra Lezaja, Andreas Panagopoulos, Yanlin Wen, Edison Carvalho, Ralph Imhof, Matthias Altmeyer
Summary: Recent studies have challenged the paradigm that checkpoints halt cell cycle progression for genome repair by discovering heritable DNA lesions escaping checkpoint control. The authors of this study have identified a new class of heritable DNA lesions marked by RPA, which are found to occur post-mitotically and exacerbated upon replication stress. Targeting post-mitotic DNA synthesis may offer a new therapeutic opportunity for ALT-positive cancer cells with high levels of replication stress and telomere fragility.
NATURE COMMUNICATIONS
(2021)
Review
Cell Biology
Devon M. Fitzgerald, Susan M. Rosenberg
Summary: The Escherichia coli SOS response to DNA damage, discovered by Evelyn Witkin and Miroslav Radman, is the prototypic DNA-damage stress response that upregulates proteins for protection and repair. Similar mechanisms are found across species and contribute to genome instability in human cancer and aging. Bacterial molecular genomic mechanisms can offer insights into universal biology, including in human disease.
Article
Multidisciplinary Sciences
Julia Su Zhou Li, Ammal Abbasi, Dong Hyun Kim, Scott M. Lippman, Ludmil B. Alexandrov, Don W. Cleveland
Summary: Epstein-Barr virus (EBV) is an oncogenic herpesvirus associated with various cancers. In this study, researchers found that the EBNA1 protein of EBV binds to a repetitive copy of an 18-base-pair imperfect palindromic sequence on human chromosome 11q23, leading to chromosome breakage. Increasing levels of EBNA1 binding trigger chromosome breakage and acquisition of structural variations in chromosome 11, which is associated with cancer development. The presence of EBV is also associated with chromosome rearrangements in various cancer types.
Article
Multidisciplinary Sciences
Kui Sun, Yunqiao Han, Jingzhen Li, Shanshan Yu, Yangjun Zhang, Jamas Reilly, Jiayi Tu, Danna Jia, Xiang Chen, Hualei Hu, Mengmeng Ren, Pei Li, Jiong Luo, Xiang Ren, Xianqin Zhang, Xinhua Shu, Fei Liu, Mugen Liu, Zhaohui Tang
Summary: This study demonstrates the necessary role of DHX38 in retinal development and reveals a novel regulatory axis involving R-loop, replication stress, and DNA damage.
Article
Medicine, Research & Experimental
Parasvi S. Patel, Karan Joshua Abraham, Kiran Kumar Naidu Guturi, Marie-Jo Halaby, Zahra Khan, Luis Palomero, Brandon Ho, Shili Duan, Jonathan St-Germain, Arash Algouneh, Francesca Mateo, Samah El Ghamrasni, Haithem Barbour, Daniel R. Barnes, Jonathan Beesley, Otto Sanchez, Hal K. Berman, Grant W. Brown, El Bachir Affar, Georgia Chenevix-Trench, Antonis C. Antoniou, Cheryl H. Arrowsmith, Brian Raught, Miquel Angel Pujana, Karim Mekhail, Anne Hakem, Razqallah Hakem
Summary: Germline mutations in BRCA1 and BRCA2 genes increase the risk of breast and ovarian cancer, while the loss of RNF168 can protect Brca1-mutant mice against mammary tumorigenesis. Studies have shown that RNF168 deficiency leads to accumulation of R-loops in BRCA1/2-mutant breast and ovarian cancer cells, causing cell death.
JOURNAL OF CLINICAL INVESTIGATION
(2021)
Article
Environmental Sciences
Anne Fernandez-Vidal, Liana C. Arnaud, Manon Maumus, Marianne Chevalier, Gladys Mirey, Bernard Salles, Julien Vignard, Elisa Boutet-Robinet
ENVIRONMENTAL AND MOLECULAR MUTAGENESIS
(2019)
Article
Gastroenterology & Hepatology
Zhen He, Raad Z. Gharaibeh, Rachel C. Newsome, Jllian L. Pope, Michael W. Dougherty, Sarah Tomkovich, Benoit Pons, Gladys Mirey, Julien Vignard, David R. Hendrixson, Christian Jobin
Article
Multidisciplinary Sciences
Benoit J. Pons, Elisabeth Bezine, Melissa Hanique, Valerie Guillet, Lionel Mourey, Johana Chicher, Teresa Frisan, Julien Vignard, Gladys Mirey
Review
Food Science & Technology
Benoit J. Pons, Julien Vignard, Gladys Mirey
Article
Food Science & Technology
Benoit J. Pons, Nicolas Loiseau, Saleha Hashim, Soraya Tadrist, Gladys Mirey, Julien Vignard
Article
Cell Biology
William Tremblay, Florence Mompart, Elisa Lopez, Muriel Quaranta, Valerie Bergoglio, Saleha Hashim, Delphine Bonnet, Laurent Alric, Emmanuel Mas, Didier Trouche, Julien Vignard, Audrey Ferrand, Gladys Mirey, Anne Fernandez-Vidal
Summary: The cytolethal distending toxin (CDT) produced by Gram-negative pathogenic bacteria can induce cell transformation, chromosomal abnormalities, and DNA damage. CDT induces replicative stress in human colorectal organoids, potentially contributing to carcinogenesis. Targeting CDT-carrying bacterial strains may be a promising therapeutic strategy for colorectal cancer patients.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Benoit J. Pons, Aurelie Pettes-Duler, Claire Naylies, Frederic Taieb, Catherine Bouchenot, Saleha Hashim, Patrick Rouimi, Maxime Deslande, Yannick Lippi, Gladys Mirey, Julien Vignard
Summary: The bacterial genotoxin CDT activates the DNA Damage Response and enhances the host immune response by promoting a strong type I interferon (IFN) response. The effects of CDT on cell cycle regulation, DNA damage, and immune response may vary depending on cell and tissue type.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2021)
Article
Food Science & Technology
Ines Abad, Julien Vignard, Catherine Bouchenot, Dimitra Graikini, Laura Grasa, Maria Dolores Perez, Gladys Mirey, Lourdes Sanchez
Summary: This study evaluated the antioxidant and antigenotoxic effects of milk-derived products in two human cell lines. The results showed that these dairy fractions significantly reversed oxidative stress and lactoferrin exhibited the highest antioxidant activity. Additionally, dairy by-products maintained their activity in a coculture of intestinal and hepatic cells, suggesting their potential use in food specialties.
