Article
Biochemistry & Molecular Biology
Sunbok Jang, Matthew A. Schaich, Cindy Khuu, Brittani L. Schnable, Chandrima Majumdar, Simon C. Watkins, Sheila S. David, Bennett Van Houten
Summary: The study reveals that UV-DDB can stimulate MUTYH turnover rate, increase complex formation between MUTYH and UV-DDB, and enhance MUTYH mobility and dissociation rate during 8-oxoG:A repair, suggesting a facilitative role of UV-DDB in MUTYH activity at abasic sites.
NUCLEIC ACIDS RESEARCH
(2021)
Editorial Material
Biochemistry & Molecular Biology
Susan E. Tsutakawa, Altaf H. Sarker
Summary: The canonical role of DNA glycosylase is in repairing global base damage, but it also plays a role in epigenetic gene regulation, immune response modulation, replication, and transcription. In this issue of Structure, Eckenroth et al. (2020) reveal the structure of NEIL2 glycosylase, showing that its catalytic domain flexibility sets it apart from other glycosylases and implies novel regulatory mechanisms.
Article
Chemistry, Analytical
Bocheng Tu, Zishan Feng, Haitao Wang, Wei Zhang, Weicong Ye, Hongbo Wang, Xianjin Xiao, Wenbo Zhao, Tongbo Wu
Summary: This new method utilizes lambda exonuclease and a background signal suppression probe, which successfully suppresses the background signal through probe structure design to achieve highly sensitive OGG detection. The detection limit is 5.0 x 10(-4) U mL(-1), and its potential clinical application value was demonstrated in biological samples.
ANALYTICA CHIMICA ACTA
(2021)
Review
Biochemistry & Molecular Biology
Luigi Magrin, Daniele Fanale, Chiara Brando, Lidia Rita Corsini, Ugo Randazzo, Marianna Di Piazza, Vittorio Gurrera, Erika Pedone, Tancredi Didier Bazan Russo, Salvatore Vieni, Gianni Pantuso, Antonio Russo, Viviana Bazan
Summary: The MUTYH gene is involved in the repair of DNA damage and its mutations are associated with colorectal polyposis and cancer. Carriers of MUTYH mutations have an increased risk of colorectal cancer and other types of tumors. Recent studies have also found an increased genetic susceptibility to cancer in carriers of monoallelic MUTYH mutations. MUTYH may also be involved in other biological functions.
Article
Multidisciplinary Sciences
Huawei Tong, Nana Liu, Yinghui Wei, Yingsi Zhou, Yun Li, Danni Wu, Ming Jin, Shuna Cui, Hengbin Li, Guoling Li, Jingxing Zhou, Yuan Yuan, Hainan Zhang, Linyu Shi, Xuan Yao, Hui Yang
Summary: Current base editors can only deaminate cytosine (C) or adenine (A), lacking the ability to edit guanine (G) or thymine (T). In this study, a deaminase-free glycosylase-based guanine base editor (gGBE) was developed by fusing Cas9 nickase with engineered N-methylpurine DNA glycosylase protein (MPG). Through mutagenesis of MPG and screening using an intron-split EGFP reporter, gGBE with engineered MPG showed over 1500-fold increase in G editing efficiency. Furthermore, this gGBE demonstrated high base editing efficiency and G-to-T or G-to-C conversion ratio in both cultured human cells and mouse embryos.
NATIONAL SCIENCE REVIEW
(2023)
Article
Biochemistry & Molecular Biology
Nadine Mueller, Andriy Khobta
Summary: The oxidation-induced DNA modification 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) has been found to interfere with gene transcription activity in two distinct ways, affecting both the promoter activity and gene expression through different mechanisms. The excision preferences of the repair enzyme OGG1 for 8-oxodG at different positions lead to varying degrees of decrease in promoter activity. The presence of different lesions at specific positions can either silence gene expression or enhance promoter activity, suggesting a role for the AP endonuclease step in regulating the switch between active and repressed promoter states during base excision repair.
Article
Biochemistry & Molecular Biology
Filipe Rollo, Patricia T. Borges, Celia M. Silveira, Margarida T. G. Rosa, Smilja Todorovic, Elin Moe
Summary: This study investigated the structure and mechanism of the three EndoIII enzymes in Deinococcus radiodurans, revealing their different activities and specificities, which is important for addressing questions regarding their presence and characteristics in the organism.
Article
Chemistry, Multidisciplinary
Liudan Jiang, Jiayong Yin, Maoxiang Qian, Shaoqin Rong, Shengqi Zhang, Kejing Chen, Chengchen Zhao, Yuanqing Tan, Jiayin Guo, Hao Chen, Siyun Gao, Tingting Liu, Yi Liu, Bin Shen, Jian Yang, Yong Zhang, Fei-Long Meng, Jinchuan Hu, Honghui Ma, Yi-Han Chen
Summary: In this study, a Ucaps-seq method was developed to detect uracil in DNA at single-nucleotide resolution. The method was proven to be highly specific and effective on synthetic DNA and real genomes. Ucaps-seq not only detected the enrichment of uracil in cells but also had potential applications in evaluating base editing fidelity.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Biochemistry & Molecular Biology
Brittany L. Carroll, Karl E. Zahn, John P. Hanley, Susan S. Wallace, Julie A. Dragon, Sylvie Doublie
Summary: Base excision repair (BER) is a key pathway in protecting cells from DNA damage caused by reactive oxygen species, with NTHL1 being a bifunctional DNA glycosylase that plays a role in repairing specific base damage; The X-ray crystal structure of hNTHL1 reveals an open conformation not seen in bacterial orthologs, with the flexibility and configuration change attributed to an interdomain linker; The large scale interdomain rearrangement during catalysis observed in hNTHL1 is unprecedented for a DNA glycosylase in the HhH superfamily, providing important insights into the molecular mechanism of this enzyme.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Gastroenterology & Hepatology
R. Patel, P. McGinty, V. Cuthill, M. Hawkins, S. K. Clark, A. Latchford
Summary: This study evaluated the outcomes of colonoscopy surveillance in carriers of MUTYH pathogenic variants, finding that this group is relatively young with a low adenoma rate and no observed cases of colorectal cancer.
INTERNATIONAL JOURNAL OF COLORECTAL DISEASE
(2021)
Article
Microbiology
Filipe Rollo, Guilherme D. Martins, Andre G. Gouveia, Solenne Ithurbide, Pascale Servant, Celia V. Romao, Elin Moe
Summary: This study demonstrates the importance of three Endonuclease III-like enzymes encoded by genes in Deinococcus radiodurans. While DrEndoIII2 is the main enzyme in this bacterium, DrEndoIII1 and 3 show unusual and undetectable activity, respectively. The knockout mutants of these genes were more resistant to oxidative stress induced by methyl viologen, indicating the crucial role of all three EndoIII homologs for cell survival. The upregulation of EndoIII homologs gene expression in response to oxidative stress may compensate for the loss of one gene.
FRONTIERS IN MICROBIOLOGY
(2023)
Article
Virology
Karen Salas-Briceno, Susan R. Ross
Summary: This study showed the critical role of UNG in removing uracils from APOBEC3-mediated MLV retroviral DNA, reducing G-to-A mutations in proviruses. The data suggest that UNG removes uracils at two stages of infection, preventing integration of viral DNA and leading to its repair or degradation.
JOURNAL OF VIROLOGY
(2021)
Article
Multidisciplinary Sciences
Peter Georgeson, Tabitha A. Harrison, Bernard J. Pope, Syed H. Zaidi, Conghui Qu, Robert S. Steinfelder, Yi Lin, Jihoon E. Joo, Khalid Mahmood, Mark Clendenning, Romy Walker, Efrat L. Amitay, Sonja Berndt, Hermann Brenner, Peter T. Campbell, Yin Cao, Andrew T. Chan, Jenny Chang-Claude, Kimberly F. Doheny, David A. Drew, Jane C. Figueiredo, Amy J. French, Steven Gallinger, Marios Giannakis, Graham G. Giles, Andrea Gsur, Marc J. Gunter, Michael Hoffmeister, Li Hsu, Wen-Yi Huang, Paul Limburg, JoAnn E. Manson, Victor Moreno, Rami Nassir, Jonathan A. Nowak, Mireia Obon-Santacana, Shuji Ogino, Amanda Phipps, John D. Potter, Robert E. Schoen, Wei Sun, Amanda E. Toland, Quang M. Trinh, Tomotaka Ugai, Finlay A. Macrae, Christophe Rosty, Thomas J. Hudson, Mark A. Jenkins, Stephen N. Thibodeau, Ingrid M. Winship, Ulrike Peters, Daniel D. Buchanan
Summary: By testing a large number of colorectal cancer patients, researchers have identified a tumor mutational signature that can accurately identify carriers of biallelic pathogenic variants in the MUTYH gene, providing important evidence for mutation classification.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Mark L. Sowers, James W. Conrad, Bruce Chang-Gu, Ellie Cherryhomes, Linda C. Hackfeld, Lawrence C. Sowers
Summary: Although genomic DNA is predominantly duplex, specific sequence motifs can favor the formation of alternative structures such as G-quadruplex. The repair of DNA damage in non-duplex structures is less understood. Placing certain pyrimidine damage products and DNA repair intermediates can affect the stability and formation of quadruplex structures. These findings provide insights into the equilibrium between duplex and quadruplex and the impact of DNA damage and repair on this equilibrium.
Article
Biochemistry & Molecular Biology
Sai Santosh Babu Komakula, Bhavya Blaze, Hong Ye, Agnieszka Dobrzyn, Harini Sampath
Summary: The BER glycosylase OGG1 plays a crucial role in modulating adipocyte differentiation and lipid accretion. Loss of OGG1 leads to increased fat accumulation in mice, while overexpression of OGG1 confers resistance to age- and diet-induced obesity. Mechanistically, changes in adipogenesis are associated with alterations in cellular PARylation, corresponding with OGG1 genotype.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Hiroki Sakamoto, Koji Miyanishi, Shingo Tanaka, Ryo Ito, Kota Hamaguchi, Akira Sakurada, Masanori Sato, Tomohiro Kubo, Takahiro Osuga, Kazuyuki Murase, Kohichi Takada, Yusaku Nakabeppu, Masayoshi Kobune, Junji Kato
Summary: The study found that MUTYH deficiency is associated with the development of liver tumors in NASH-related conditions. In mouse experiments, MUTYH-null mice fed a high-fat high-cholesterol+high-iron diet were more likely to develop liver tumors and showed higher accumulation of oxidative stress markers. Gene expression analysis also indicated involvement of the Wnt/beta-catenin signaling pathway and increased c-Myc expression in MUTYH-null liver tissues.
SCIENTIFIC REPORTS
(2021)
Article
Multidisciplinary Sciences
Sugako Oka, Julio Leon, Kunihiko Sakumi, Nona Abolhassani, Zijing Sheng, Daisuke Tsuchimoto, Frank M. LaFerla, Yusaku Nakabeppu
Summary: 8-Oxoguanine accumulates in Alzheimer's disease brains, and deficiency of MTH1 and OGG1 can increase its accumulation, leading to microglial activation and neuronal loss. Minocycline can inhibit microglial activation and reduce neuroinflammation, providing a potential new approach for preventing and treating AD.
SCIENTIFIC REPORTS
(2021)
Article
Cell Biology
Guianfranco Mazzei, Ryohei Ikegami, Nona Abolhassani, Naoki Haruyama, Kunihiko Sakumi, Takashi Saito, Takaomi C. Saido, Yusaku Nakabeppu
Summary: The study found that high-fat diet caused cognitive impairment, increased A beta deposition, and microgliosis in transgenic mouse models of Alzheimer's disease, accompanied by insulin resistance in the hippocampus.
Article
Biochemistry & Molecular Biology
Teruya Nakamura, Kohtaro Okabe, Shogo Hirayama, Mami Chirifu, Shinji Ikemizu, Hiroshi Morioka, Yusaku Nakabeppu, Yuriko Yamagata
Summary: MUTYH is a crucial DNA repair enzyme, and mutations associated with colorectal cancer can lead to MAP disease. Studies have shown that MUTYH participates in base excision repair with PCNA during DNA replication and contains a binding motif related to proteins involved in DNA damage response.
NUCLEIC ACIDS RESEARCH
(2021)
Correction
Multidisciplinary Sciences
Erika Castillo, Julio Leon, Guianfranco Mazzei, Nona Abolhassani, Naoki Haruyama, Takashi Saito, Takaomi Saido, Masaaki Hokama, Toru Iwaki, Tomoyuki Ohara, Toshiharu Ninomiya, Yutaka Kiyohara, Kunihiko Sakumi, Frank M. LaFerla, Yusaku Nakabeppu
SCIENTIFIC REPORTS
(2021)
Article
Clinical Neurology
Yukino Miyachi, Takayuki Fujii, Ryo Yamasaki, Daisuke Tsuchimoto, Kyoko Iinuma, Ayako Sakoda, Shoko Fukumoto, Takuya Matsushita, Katsuhisa Masaki, Noriko Isobe, Yusaku Nakabeppu, Jun-ichi Kira
Summary: This study aimed to investigate the impact of serum anti-oligodendrocyte antibodies on the clinical features of MS patients and validate whether these antibodies could serve as biomarkers for CNS tissue damage in MS patients. Results showed that anti-oligodendrocyte antibodies were positive in PPMS and SPMS patients, while absent in RRMS, NMOSD, OIND patients, and healthy controls.
FRONTIERS IN NEUROLOGY
(2021)
Article
Biochemistry & Molecular Biology
Jingwen Chen, Xin Wu, Yanyi Wang, Yunfeng Pan, Yan Ren, Yusaku Nakabeppu, Yimei Fan, Yaping Wang
Summary: This study demonstrates that Mutyh deficiency can lead to changes in mitochondrial structure and impair mitochondrial function through downregulation of Mfn2 and alteration of the ratio of L-Opa1/S-Opa1, accompanied by a reduction in alpha-ketoglutaric acid (alpha-KG). Further analysis reveals that Mutyh deficiency may cause downregulation of histone demethylases and DNA demethylases and inhibition of Mfn2 transcription. Interestingly, supplementation of alpha-KG can alleviate the damage associated with Mutyh deficiency, restore Mfn2 expression, and prevent degradation of L-Opa1.
FREE RADICAL RESEARCH
(2022)
Correction
Biochemistry & Molecular Biology
Takashi Ishii, Tatsuhiro Igawa, Hiroshi Hayakawa, Tsugumi Fujita, Mutsuo Sekiguchi, Yusaku Nakabeppu
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Neurosciences
Yuri Mizuno, Nona Abolhassani, Guianfranco Mazzei, Takashi Saito, Takaomi C. Saido, Ryo Yamasaki, Jun-ichi Kira, Yusaku Nakabeppu
Summary: Oxidative stress is a major risk factor for Alzheimer's disease, characterized by the accumulation of 8-oxoG in the brain. Deficiency of MTH1 and OGG1 accelerates the accumulation of 8-oxoG in DNA and leads to reduced anxiety-related behavior in 6-month-old mice.
NEUROSCIENCE RESEARCH
(2022)
Article
Cell Biology
Yuri Mizuno, Nona Abolhassani, Guianfranco Mazzei, Kunihiko Sakumi, Takashi Saito, Takaomi C. Saido, Toshiharu Ninomiya, Toru Iwaki, Ryo Yamasaki, Jun-ichi Kira, Yusaku Nakabeppu
Summary: Oxidative stress is a major risk factor for Alzheimer's disease, and MUTYH plays a key role in minimizing DNA damage caused by oxidative stress. The deficiency of MUTYH improves memory impairment by reducing microgliosis and enhancing neurogenesis in AD model mice.
OXIDATIVE MEDICINE AND CELLULAR LONGEVITY
(2021)
Article
Cell Biology
Chukwuemeka George Anene-Nzelu, Peter Yiqing Li, Tuan Danh Anh Luu, Shi Ling Ng, Zenia Tiang, Bangfen Pan, Wilson Lek Wen Tan, Matthew Ackers-Johnson, Ching Kit Chen, Yee Phong Lim, Rina Wang Miao Qin, Wee Woon Chua, Lim Xin Yi, Roger Sik-Yin Foo, Yusaku Nakabeppu
Summary: Doxorubicin, commonly used for cancer treatment, can cause cardiotoxicity. This study demonstrates that deficiency of OGG1 gene exacerbates doxorubicin-induced cardiac dysfunction and increases mortality in mice. Transcriptomic analysis reveals dysregulation of genes related to inflammation in the hearts of Ogg1 knockout mice.
OXIDATIVE MEDICINE AND CELLULAR LONGEVITY
(2022)
Article
Psychiatry
Kazuya Matsuo, Yasuharu Shinoda, Nona Abolhassani, Yusaku Nakabeppu, Kohji Fukunaga
Summary: This study explored molecular alterations in the hippocampus of rats with autism spectrum disorder (ASD) and the effects of chronic administration of intranasal oxytocin (OXT). The results revealed that prenatal valproic acid (VPA) exposure altered gene expression in the hippocampus, with some of these genes suggested as candidates for ASD and involved in memory, developmental processes, and epilepsy. OXT treatment partly improved the expression of these genes, which interacted with genes involved in social behaviors and hippocampal-dependent memory.
FRONTIERS IN PSYCHIATRY
(2022)
Article
Biochemistry & Molecular Biology
Teruya Nakamura, Yukari Koga-Ogawa, Kana Fujimiya, Mami Chirifu, Masataka Goto, Shinji Ikemizu, Yusaku Nakabeppu, Yuriko Yamagata
Summary: The human MTH1 protein recognizes substrates through the exchange of protonation states, and the protonation state change is related to its substrate binding ability.
Article
Neurosciences
Sayaka Okuzono, Fumihiko Fujii, Yuki Matsushita, Daiki Setoyama, Yohei Shinmyo, Ryoji Taira, Kousuke Yonemoto, Satoshi Akamine, Yoshitomo Motomura, Masafumi Sanefuji, Takeshi Sakurai, Hiroshi Kawasaki, Kihoon Han, Takahiro A. Kato, Hiroyuki Torisu, Dongchon Kang, Yusaku Nakabeppu, Yasunari Sakai, Shouichi Ohga
Summary: Epileptic seizures are common comorbidities in children with autism spectrum disorder (ASD), but little is known about the genes involved and their role in regulating neuronal excitability. This study found that Shank3, an ASD-associated gene, plays a unique role in protecting thalamocortical neurons from hyperexcitability during the early postnatal period. These findings have important implications for understanding the mechanisms underlying seizures in children with autism.
NEUROSCIENCE RESEARCH
(2023)
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.