Review
Plant Sciences
Jose Antonio Pedroza-Garcia, Yanli Xiang, Lieven De Veylder
Summary: Plants utilize DNA damage response pathways to cope with various stresses, involving cell cycle checkpoint mechanisms that either pause the cell cycle for DNA repair or direct cells into differentiation or programmed cell death. Different checkpoint mechanisms control replication processes and G2/M transition, with plant-specific elements such as SOG1 playing a key role. These mechanisms are called upon during development, signaling pathways, and in response to stresses, contributing to plant adaptation to changing environments.
Article
Cell Biology
Sargun Sokhi, Cody W. Lewis, Amirali B. Bukhari, Joanne Hadfield, Edric J. Xiao, Jeremy Fung, Yea Jin Yoon, Wen-Hsin Hsu, Armin M. Gamper, Gordon K. Chan
Summary: Cell cycle checkpoint kinases are important targets for cancer therapy, and their inhibition can induce cell death or increase sensitivity to other genotoxic therapies. In this study, the researchers found that the overexpression of Myt1, a kinase regulating cell cycle progression, confers resistance to inhibitors of other kinases. Elevated Myt1 levels compensate for Cdk1 inhibition and lead to reduced premature mitotic entry and decreased length of mitosis, ultimately increasing cell survival rates. The findings suggest that Myt1 overexpression is a common mechanism by which cancer cells acquire resistance to drugs targeting the G2/M checkpoint.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Naomie Gentric, Pascal Genschik, Sandra Noir
Summary: The article discusses the response of plants to DNA damage, summarizing important regulatory steps of the plant cell cycle and DNA damage response mechanisms. Furthermore, it specifically examines the role played by some cell cycle regulators at the interface between the cell cycle and DNA damage responses.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cell Biology
Indra A. Shaltiel, Alba Llopis, Melinda Aprelia, Rob Klompmaker, Apostolos Menegakis, Lenno Krenning, Rene H. Medema
Summary: Most Cdks are redundant for normal cell division, but become essential for S-phase entry after DNA damage in G1. In damaged cells, high levels of Cdk4/6 activity are required to inactivate pocket proteins and APC/C-Cdh1 to promote the transition from G1 to S phase.
Article
Biochemistry & Molecular Biology
Mateusz Kciuk, Adrianna Gieleci, Somdutt Mujwar, Mariusz Mojzych, Renata Kontek
Summary: The cyclin-dependent kinase (CDK) family plays a critical role in regulating transcription and cell-cycle progression. Recent studies have revealed their involvement in DNA damage response (DDR) and repair, impacting the fidelity of cell division and maintenance of genomic integrity.
BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER
(2022)
Review
Oncology
Siyao Deng, Tijana Vlatkovic, Moying Li, Tianzuo Zhan, Marlon R. Veldwijk, Carsten Herskind
Summary: This review focuses on the role of DNA damage response and repair pathways in radiotherapy, and the potential for enhancing the sensitivity of colorectal cancer to radiotherapy by targeting cell-cycle checkpoint proteins.
Article
Biochemistry & Molecular Biology
Thomas Eekhout, Jose Antonio Pedroza-Garcia, Pooneh Kalhorzadeh, Geert De Jaeger, Lieven De Veylder
Summary: During DNA replication, the WEE1 kinase inhibits cyclin-dependent kinases (CDKs) to safeguard genomic integrity. Wee1 mutant plants are hypersensitive to replication stress due to their inability to respond properly to DNA replication problems. The pol alpha-2 mutant, with a mutated catalytic subunit of DNA polymerase alpha, acts as a suppressor mutant of wee1 by causing instability and interaction loss, leading to a prolonged S-phase.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Microbiology
Inma Quilis, Merce Gomar-Alba, Juan Carlos Igual
Summary: The CWI pathway in yeast is activated in response to environmental stresses and morphogenetic processes, regulating cell-wall biosynthesis and actin cytoskeleton during periods of polarized growth. Additionally, it plays a role in delaying cell-cycle progression during cell-surface perturbance, affecting key transitions like Start transcriptional program, DNA replication, and mitosis. The CWI pathway also contributes to the response to genotoxic stress and is connected to the DNA integrity checkpoint, serving as a master brake to stop cell-cycle progression under unfavorable conditions.
Article
Cell & Tissue Engineering
Miriama Kruta, Mary Jean Sunshine, Bernadette A. Chua, Yunpeng Fu, Ashu Chawla, Christopher H. Dillingham, Lorena Hidalgo San Jose, Bijou De Jong, Fanny J. Zhou, Robert A. J. Signer
Summary: Maintaining proteostasis is crucial for preserving stem cell function, but mechanisms regulating proteostasis during stress in stem cells and its contribution to stem cell aging need further exploration. Activation of Hsf1 with small molecules can partially suppress protein synthesis, rebalance proteostasis, and support the regenerative activity of HSCs, indicating that Hsf1 promotes proteostasis and regenerative capacity in response to stress and aging.
Article
Respiratory System
Quan Li, Pan Zhang, Huixiao Hu, Hang Huang, Dong Pan, Guangyun Mao, Burong Hu
Summary: In this study, a prognostic model based on 4 DDR-related genes with cell cycle checkpoint function was constructed to predict the survival rate, immune activity, and chemoradiotherapy responsiveness of LUAD patients.
RESPIRATORY RESEARCH
(2022)
Article
Plant Sciences
Wen-Jie Zheng, Wang-Qing Li, Yan Peng, Ye Shao, Li Tang, Ci-Tao Liu, Dan Zhang, Lan-Jing Zhang, Ji-Huan Li, Wu-Zhong Luo, Zhi-Cheng Yuan, Bing-Ran Zhao, Bi-Gang Mao
Summary: In this study, the expression changes and interaction between rice E2Fs and OsMSHs under cadmium stress were systematically investigated. It was found that cadmium stress may regulate the expression of OsMSHs by affecting the cell cycle, resulting in an enhanced response to cadmium stress.
FRONTIERS IN PLANT SCIENCE
(2022)
Article
Genetics & Heredity
Yuan Wang, Shoji Oda, Masataka G. Suzuki, Hiroshi Mitani, Fugaku Aoki
Summary: Mammalian zygotes have higher sensitivity to radiation due to defective DNA damage response (DDR) at G1, S, and M phases. This study irradiated mouse zygotes at different cell cycle phases and found that DNA damage checkpoints were activated only at the G2 phase. The absence of DNA damage checkpoints at G1 and M phases may be due to low phosphorylated CHK2 levels. The low developmental rates of embryos irradiated at G1, S, and M phases suggest that these embryos are prone to developmental failure due to chromatin abnormalities.
Article
Biochemistry & Molecular Biology
Hanchen Chen, Ting Pan, Xueao Zheng, Yongchi Huang, Chong Wu, Tongbin Yang, Shan Gao, Lili Wang, Shunping Yan
Summary: DNA replication stress is a threat to genome stability and is a characteristic feature of cancer in humans. The kinases ATR and WEE1 are essential for activating the replication stress responses. This study demonstrates that ATR-WEE1 inhibits GCN20-GCN1 activity to promote the translation of the master transcription factor, SOG1, during replication stress in Arabidopsis.
Review
Plant Sciences
Akie Shimotohno, Shiori S. Aki, Naoki Takahashi, Masaaki Umeda
Summary: This review highlights the importance of plant cell cycle regulation by phytohormones and environmental signals, analyzing their mechanisms of action and focusing on stress-induced G2 arrest. It also discusses the contribution of the transition from the mitotic cycle to the endocycle to plant organ growth.
ANNUAL REVIEW OF PLANT BIOLOGY, VOL 72, 2021
(2021)
Article
Cell Biology
Ines Faleiro, Ana I. Afonso, Andre Balsinha, Beatriz Lucas, Robert M. Martin, Edgar R. Gomes, Sergio F. de Almeida
Summary: This study investigates the dynamics of DNA damage response (DDR) during cellular differentiation using an in vitro model. The findings reveal that differentiated skeletal muscle cells have a prolonged DDR but are competent in repairing DNA breaks and enhancing cell survival. The study also uncovers the strategies employed by the muscle cells to maintain genetic integrity and organ function after DNA damage.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Takuya Honda, Kaisei Motoyoshi, Junya Kasahara, Kazuyuki Yamagata, Hiromasa Takahashi, Hiroyuki Nakamura, Toshihiko Murayama
Summary: This study demonstrates that the expression of v-Src up-regulates GCS activity through tyrosine phosphorylation in a post-translational manner. The research also reveals the crucial impact of regulating GCS activity on ceramide-induced cytotoxicity through studying GCS mutations.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
(2021)
Article
Pharmacology & Pharmacy
Hitomi Ashikawa, Hinako Mogi, Takuya Honda, Hiroyuki Nakamura, Toshihiko Murayama
Summary: NPC is caused by a loss of function of NPC1 or NPC2 protein, leading to accumulation of free-cholesterol in cells and resulting in cell damage and neurodegenerative disease. Antiepileptic drug primidone may enhance free-cholesterol trafficking in NPC cells, potentially offering a treatment option for NPC.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2021)
Article
Cell Biology
Ryuzaburo Yuki, Mari Hagino, Sachi Ueno, Takahisa Kuga, Youhei Saito, Yasunori Fukumoto, Noritaka Yamaguchi, Naoto Yamaguchi, Yuji Nakayama
Summary: v-Src alters the cytotoxicities of microtubule-targeting agents (MTAs) and polo-like kinase 1 (PLK1) inhibitor, but not DNA-damaging anticancer drugs. It induces mitotic slippage of MTAs-treated cells, leading to the generation of proliferating tetraploid cells. Treatment with Aurora kinase inhibitor strongly induces cell death in cells expressing v-Src.
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Jie Bai, Takako Yokomizo-Nakano, Sho Kubota, Yuqi Sun, Akinori Kanai, Mihoko Iimori, Hironori Harada, Atsushi Iwama, Goro Sashida
Summary: High Mobility Group AT-hook 2 (HMGA2) is found to be overexpressed in patients with myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), with its expression level finely tuned by Lin28b-Let-7 axis and Polycomb Repressive Complex 2. The overexpression of HMGA2 can activate the oncogene Igf2bp2 and enhance self-renewal of Tet2-deficient stem cells, affecting the transcriptional program and differentiation of myeloid cells. These findings highlight the potential therapeutic target of HMGA2-Igf2bp2 axis in the transformation of stem cells.
Article
Multidisciplinary Sciences
Mariko Morii, Sho Kubota, Chizu Hasegawa, Yumi Takeda, Shiori Kometani, Kyoko Enomoto, Takayuki Suzuki, Sayuri Yanase, Rika Sato, Aki Akatsu, Kensuke Hirata, Takuya Honda, Takahisa Kuga, Takeshi Tomonaga, Yuji Nakayama, Noritaka Yamaguchi, Naoto Yamaguchi
Summary: The Src-family tyrosine kinases (SFKs) accumulate in the centrosome region at the beginning of mitosis and phosphorylate PRC1 and kinastrin, leading to their delocalization from microtubules during mitosis.
SCIENTIFIC REPORTS
(2021)
Article
Cell Biology
Tadahito Yasuda, Mayu Koiwa, Atsuko Yonemura, Keisuke Miyake, Ryusho Kariya, Sho Kubota, Takako Yokomizo-Nakano, Noriko Yasuda-Yoshihara, Tomoyuki Uchihara, Rumi Itoyama, Luke Bu, Lingfeng Fu, Kota Arima, Daisuke Izumi, Shiro Iwagami, Kojiro Eto, Masaaki Iwatsuki, Yoshifumi Baba, Naoya Yoshida, Hiroto Ohguchi, Seiji Okada, Keisuke Matsusaki, Goro Sashida, Akiko Takahashi, Patrick Tan, Hideo Baba, Takatsugu Ishimoto
Summary: In the tumor microenvironment, senescent cancer-associated fibroblasts (CAFs) play a role in promoting gastric cancer (GC) peritoneal tumor formation through maintenance of the senescence-associated secretory phenotype (SASP) and JAK/STAT3 signaling. Single-cell mass cytometry analysis revealed a high expression level of senescent fibroblasts and SASP factors in the ascites of GC patients. These findings provide insights into the molecular mechanisms of inflammation-related SASP maintenance and the involvement of senescent CAFs in GC peritoneal dissemination.
Letter
Oncology
Mohamed Gaber Abdallah, Akiko Niibori-Nambu, Mariko Morii, Takako Yokomizo, Tomomasa Yokomizo, Takako Ideue, Sho Kubota, Vania Swee Imm Teoh, Michelle Meng Huang Mok, Chelsia Qiuxia Wang, Abdellah Ali Omar, Kenji Tokunaga, Eisaku Iwanaga, Masao Matsuoka, Norio Asou, Naomi Nakagata, Kimi Araki, Mabrouk AboElenin, Sayed Hamada Madboly, Goro Sashida, Motomi Osato
Article
Pharmacology & Pharmacy
Zhihui Tang, Kaisei Motoyoshi, Takuya Honda, Hiroyuki Nakamura, Toshihiko Murayama
Summary: Sphingolipids, such as ceramide, play important roles in brain and tissue development. Disruption of sphingolipid homeostasis, particularly up-regulation of ceramide, is involved in diseases like Alzheimer's. Specifically, A beta(25-35) induced cytotoxicity is partially mediated by inhibiting GIcCer synthase activity.
BIOLOGICAL & PHARMACEUTICAL BULLETIN
(2021)
Article
Biochemistry & Molecular Biology
Terumasa Umemoto, Alban Johansson, Shah Adil Ishtiyaq Ahmad, Michihiro Hashimoto, Sho Kubota, Kenta Kikuchi, Haruki Odaka, Takumi Era, Daisuke Kurotaki, Goro Sashida, Toshio Suda
Summary: By studying the mitochondrial metabolism and ATP citrate lyase (ACLY) in hematopoietic stem cells (HSCs), we have gained new insights into the regulation of HSCs during hematopoietic regeneration.
Article
Biochemistry & Molecular Biology
Supannika Sorin, Sho Kubota, Sofiane Hamidi, Takako Yokomizo-Nakano, Kulthida Vaeteewoottacharn, Sopit Wongkham, Sakda Waraasawapati, Chawalit Pairojkul, Jie Bai, Mariko Morii, Guojun Sheng, Kanlayanee Sawanyawisuth, Goro Sashida
Summary: This study found that the high expression of high mobility group nucleosome-binding protein 3 (HMGN3) is correlated with the metastasis of cholangiocarcinoma (CCA). HMGN3 inhibits the expression of epithelial regulator genes by binding with the transcription factor SNAI2 and regulating histone deacetylases (HDACs), thereby affecting the migration capacity of CCA cells.
Article
Biochemistry & Molecular Biology
Masato Mashimo, Momoko Kita, Arina Uno, Moe Nii, Moe Ishihara, Takuya Honda, Yuka Gotoh-Kinoshita, Atsuo Nomura, Hiroyuki Nakamura, Toshihiko Murayama, Ryoichi Kizu, Takeshi Fujii
Summary: Poly(ADP-ribosyl)ation is a post-translational modification process that transfers poly(ADP-ribose) to proteins. TNKS1/2 have been found to play important roles in neuronal development, promoting neurite outgrowth and synapse formation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Medicine, Research & Experimental
Ai Tanaka, Kohei Anada, Masataka Yasue, Takuya Honda, Hiroyuki Nakamura, Toshihiko Murayama
Summary: Changes in sphingolipid metabolism in the brain can affect various cellular functions. In this study, we investigated the roles of CerK and C1P in multiple sclerosis. Our results showed that CerK knockout improved motor dysfunction and demyelination in a multiple sclerosis mouse model. Additionally, CerK knockout also had an impact on gender differences in mice.
Article
Pharmacology & Pharmacy
Ai Tanaka, Takuya Honda, Masataka Yasue, Risa Yamazaki, Hiroto Hatakeyama, Akihiro Hisaka, Masato Mashimo, Takafumi Kohama, Hiroyuki Nakamura, Toshihiko Murayama
Summary: This study investigated the effects of CerK/C1P pathway on the onset and progression of sepsis-related events in LPS-treated sepsis-model mice. The results showed that CerK knockout increased the lethality in mice and affected the levels of various immune/inflammation-related molecules.
JOURNAL OF PHARMACOLOGICAL SCIENCES
(2022)
Article
Immunology
Takako Yokomizo-Nakano, Ai Hamashima, Sho Kubota, Jie Bai, Supannika Sorin, Yuqi Sun, Kenta Kikuchi, Mihoko Iimori, Mariko Morii, Akinori Kanai, Atsushi Iwama, Gang Huang, Daisuke Kurotaki, Hitoshi Takizawa, Hirotaka Matsui, Goro Sashida
Summary: Prior infection stress and loss of Tet2 gene can remodel the transcriptional and epigenetic landscapes and cellular functions in hematopoietic stem cells (HSCs) via the Trif-Plk-Elf1 axis and drive the development of myelodysplastic syndrome (MDS). Pharmacological inhibition of Plk function or knockdown of Elf1 expression can prevent epigenetic remodeling in HSCs and alleviate clonogenicity enhancement and impaired erythropoiesis. Additionally, the Elf1-target signature is significantly enriched in MDS HSPCs in humans.
JOURNAL OF EXPERIMENTAL MEDICINE
(2023)
Article
Genetics & Heredity
Yasunori Fukumoto, Tyuji Hoshino, Yuji Nakayama, Yasumitsu Ogra
Summary: The ATR pathway is essential for maintaining genome integrity and is a potential target for cancer treatment. This study reveals a novel molecular interface, iVERGE, between the Rad17-RFC2-5 and 9-1-1 complexes, and suggests that Rad17 utilizes two distinct molecular interfaces to regulate the 9-1-1 complex.