Review
Pharmacology & Pharmacy
Randi J. Hagerman, Paul J. Hagerman
Summary: Fragile X syndrome is a common form of inherited intellectual disability and autism spectrum disorder, caused by large expansions of noncoding CGG repeats in the FMR1 gene. While there is currently no direct way to reverse the loss of FMRP, there is potential for effective treatments targeting dysregulated pathways in the near future.
ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Xu Zheng, Wenhe Zhang, Yinchao Hu, Zhexuan Zhao, Jiaxin Wu, Xiaoqing Zhang, Fengqi Hao, Jinling Han, Jing Xu, Wenjing Hao, Ruoxi Wang, Meihong Tian, Zsolt Radak, Yusaku Nakabeppu, Istvan Boldogh, Xueqing Ba
Summary: Exercise-induced generation of 8-oxoG promotes muscle remodeling and adaptation by activating the Ras-MEK-MyoD signal pathway. This study reveals the signaling role of DNA repair metabolite 8-oxoG in muscle remodeling and adaptation, and suggests its potential therapeutic application in muscle damage-related disorders.
Article
Medicine, General & Internal
Maria Isabel Alvarez-Mora, Ines Agusti, Robin Wijngaard, Estefania Martinez-Barrios, Tamara Barcos, Aina Borras, Sara Peralta, Marta Guimera, Ana Goday, Dolors Manau, Laia Rodriguez-Revenga
Summary: The study found a significant association between FXPOI and high expression levels of FMR4 in female FMR1 premutation carriers, suggesting a potential role of FMR4 as a biomarker for FXPOI.
JOURNAL OF CLINICAL MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Cheyenne N. Phillips, Shawn Schowe, Conner J. Langeberg, Namoos Siddique, Erich G. Chapman, Marino J. E. Resendiz
Summary: The research shows that the exonuclease Xrn-1 stalls when encountering RNA with 8-oxoG, possibly due to spatial constraints and conformational changes. However, these factors alone do not fully explain the higher stalling yields observed, suggesting that additional factors like altered pi-pi stacking and induced H-bonding interactions may also contribute to the decreased Xrn-1 efficiency.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2021)
Article
Genetics & Heredity
Andrea M. Kaminski, Thomas A. Kunkel, Lars C. Pedersen, Katarzyna Bebenek
Summary: 8-oxo-guanine (8OG) is a common base lesion associated with human diseases such as cancer, aging-related neurodegenerative disorders, and atherosclerosis. It is highly mutagenic and poses challenges for DNA polymerases in replicating and repairing genomic or mitochondrial DNA correctly.
Article
Pathology
Elizabeth Berry-Kravis, Lili Zhou, Jonathan Jackson, Flora Tassone
Summary: The novel CGG repeat primed FMR1 PCR assay designed in 2009 allows consistent detection of large full mutation alleles, resolution of heterozygosity in females, and mapping of AGG interspersions. The AmplideX Fragile X Dx and Carrier Screen Kit has been validated for FDA approval, showing high accuracy and efficiency in determining FMR1 allele size. This assay is considered a highly accurate and time-efficient method for FMR1 allele size determination, with limitations including no methylation assessment and difficulty in detecting full mutation peaks in some mosaic samples.
EXPERT REVIEW OF MOLECULAR DIAGNOSTICS
(2021)
Article
Multidisciplinary Sciences
Marlinde L. van den Boogaard, Rurika Oka, Anne Hakkert, Linda Schild, Marli E. Ebus, Michael R. van Gerven, Danny A. Zwijnenburg, Piet Molenaar, Lieke L. Hoyng, M. Emmy M. Dolman, Anke H. W. Essing, Bianca Koopmans, Thomas Helleday, Jarno Drost, Ruben van Boxtel, Rogier Versteeg, Jan Koster, Jan J. Molenaar
Summary: Neuroblastomas, childhood tumors, exhibit a high frequency of somatic C > A substitutions associated with poor survival. Defects in 8-oxoG repair in neuroblastoma lead to accumulation of C > A substitutions, contributing to mutagenesis and tumor evolution.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biochemistry & Molecular Biology
Hun-Goo Lee, Sachiko Imaichi, Elizabeth Kraeutler, Rodrigo Aguilar, Yong-Woo Lee, Steven D. Sheridan, Jeannie T. Lee
Summary: In this article, we describe an approach to correct the genetic defect in fragile X syndrome (FXS) through the recruitment of endogenous repair mechanisms. By investigating conditions favorable to FMR1 reactivation, we identify MEK and BRAF inhibitors that induce a strong repeat contraction and full FMR1 reactivation in cellular models. This study reveals a potential method of treating FXS in the future by recruiting endogenous DNA repair mechanisms.
Article
Neurosciences
Steven Colvin, Nick Lea, Qiangge Zhang, Martin Wienisch, Tobias Kaiser, Tomomi Aida, Guoping Feng
Summary: This study suggests that the length of CGG repeat in mouse models is unlikely to be the main factor preventing methylation and alternative models closer to humans may be required to effectively study FXS.
Article
Biochemistry & Molecular Biology
Trine Henriksen, Allan Weimann, Emil List Larsen, Henrik Enghusen Poulsen
Summary: The analysis methods for 8-oxodGuo and 8-oxoGuo in plasma have not been established, and the existing plasma values in literature vary greatly. A new liquid chromatography mass spectrometry method allows estimation of 8-oxoGuo production from a single plasma sample, but the measurement methods for 8-oxodGuo remains controversial.
FREE RADICAL BIOLOGY AND MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Danuta Z. Loesch, Flora Tassone, Anna Atkinson, Paige Stimpson, Nicholas Trost, Dean L. Pountney, Elsdon Storey
Summary: Expansions of the CGG repeat in the non-coding segment of the FMR1 X-linked gene are associated with various phenotypic changes. Female carriers of the fragile X premutation may themselves experience a wide range of clinical problems, with the most severe being Fragile X-Associated Tremor Ataxia Syndrome (FXTAS). Male premutation carriers have a higher risk of developing FXTAS, but sex-specific differences in clinical manifestations and progression are poorly documented.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Elisabetta Tabolacci, Veronica Nobile, Cecilia Pucci, Pietro Chiurazzi
Summary: A dynamic mutation in the FMR1 gene leads to Fragile X-related Disorders, primarily due to the expansion of an unstable CGG repeat sequence. Expansion events of the CGG sequence are more common than contractions, and the formation of abnormal secondary DNA structures may contribute to CGG expansion.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Medical Laboratory Technology
Yutong Zou, Xiaoli Ma, Songlin Yu, Ling Qiu
Summary: The necessity of pre-heating frozen urine samples for the accurate determination of 8-oxoG and 8-oxodG is currently unclear. This study suggests that pre-heating the samples may not always be necessary for the accurate measurement of these markers, depending on the pre-treatment and determination methods.
JOURNAL OF CLINICAL LABORATORY ANALYSIS
(2022)
Article
Environmental Sciences
Teresa Urbano, Tommaso Filippini, Lauren A. Wise, Sabrina Sucato, Elisa Polledri, Marcella Malavolti, Silvia Fustinoni, Bernhard Michalke, Marco Vinceti
Summary: This study assessed the association between selenium status and urinary 8-oxodG concentrations in a Northern Italian population and found that this association varied by sex, with background exposure to selenium species positively associated with oxidative stress.
SCIENCE OF THE TOTAL ENVIRONMENT
(2023)
Article
Chemistry, Physical
Leonardo Vetritti, Janina Kopyra, Paulina Wierzbicka, Maircio T. do N. Varella
Summary: 8-oxo-Guanine is a mutagenic lesion that results from reactions between reactive oxygen species and guanine in DNA. The electron-induced fragmentation of 8-oxo-guanine is remarkably different from the native form, and more complex reactions were observed, potentially producing several anion fragments at very low energies.
JOURNAL OF PHYSICAL CHEMISTRY A
(2023)
