Article
Biochemistry & Molecular Biology
Sonia Paget, Marion Dubuissez, Adeline Page, Vanessa Dehennaut, Ingrid Loison, Nathalie Spruyt, Dominique Leprince
Summary: HIC1 is a tumor suppressor gene encoding a transcriptional repressor that plays a role in the DNA-damage response. Specific posttranslational modifications, such as phosphorylation and acetylation, are crucial for the function of HIC1 and its activity in DNA repair. These modifications are essential for HIC1-mediated cellular response to repairable DNA double strand breaks.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Food Science & Technology
Silu Hou, Yuqiang Cheng, Zhaofei Wang, Luming Xia, Jian Wang, Hengan Wang, Jianhe Sun, Jingjiao Ma, Yaxian Yan
Summary: This study investigated the toxic effects of deoxynivalenol (DON) on gastric mucosal epithelial cells and found that DON can inhibit cell activity, induce DNA damage, apoptosis, and cell cycle arrest. These findings are important for understanding the cytotoxicity and gastric diseases caused by DON.
FOOD AND CHEMICAL TOXICOLOGY
(2023)
Article
Oncology
Amr Ghaleb, Lucia Roa, Natalia Marchenko
Summary: The biological consequences of low-dose radiation (LDR) in breast cancer are unclear, while high-dose radiation (HDR) promotes DNA repair and cell cycle arrest. Mutant p53 promotes mammary tumorigenesis following LDR, but has negligible effects on tumors carrying the wild-type p53 allele.
Article
Cell Biology
Sheema Almozyan, James Coulton, Roya Babaei-Jadidi, Abdolrahman S. Nateri
Summary: Recent studies have indicated that FLYWCH1 may play a critical role in facilitating the recruitment of DNA-damage response proteins in the context of DNA damage and repair.
Article
Multidisciplinary Sciences
Shantanu Gupta, Pritam Kumar Panda, Ronaldo F. Hashimoto, Shailesh Kumar Samal, Suman Mishra, Suresh Kr Verma, Yogendra Kumar Mishra, Rajeev Ahuja
Summary: Transfection of tumor suppressor miRNAs, such as miR-34a, miR-449a, and miR-16, can regulate apoptosis, senescence, and autophagy in cancer cells. However, the specific functions of miR-34a and miR-449a in autophagy and the cooperative or individual roles of these three miRNAs in the functional G1/S checkpoint signaling pathways in HeLa cells remain unknown. This study presents a synthetic Boolean network illustrating the regulatory effects of these miRNAs and demonstrates their advanced role in cervical cancer signaling pathways.
SCIENTIFIC REPORTS
(2022)
Article
Biochemistry & Molecular Biology
Huan Liu, Wenchao Zhang, Lijie Jin, Shasha Liu, Liying Liang, Yanfei Wei
Summary: This study investigates the anticancer mechanism of Plumbagin (PLB) and its potential connections with oxidative stress, genotoxicity, and cell cycle arrest. The results indicate that PLB significantly inhibits HCC cell viability and colony formation, induces G2/M cell cycle arrest, oxidative stress, and DNA damage. These effects can be attenuated by NAC pretreatment. PLB triggers a DNA damage response by activating ATM, Chk1, Chk2, and p53. Furthermore, the key modulator of the G2/M transition factor, cdc25C, is downregulated in an ROS-dependent manner. Inhibition of the ATM-p53 pathway can reduce the occurrence of G2/M cell cycle arrest. Therefore, ROS-mediated oxidative stress plays a crucial role in PLB-induced G2/M cell cycle arrest mediated by the ATM-p53 pathway.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biology
Yang Wei, Ruilin Bao, Le Hu, Yanqing Geng, Xuemei Chen, Yixian Wen, Yingxiong Wang, Mao Qin, Yue Zhang, Xueqing Liu
Summary: This study evaluated the reproductive toxicity of two-dimensional ultrathin Ti3C2 nanosheets in the testes. It found that exposure to Ti3C2 nanosheets caused defects in spermatogenic function, possibly due to oxidative stress and DNA damage.
Article
Cell Biology
Miaoqin Chen, Weikai Wang, Shiman Hu, Yifan Tong, Yiling Li, Qi Wei, Lei Yu, Liyuan Zhu, Yiran Zhu, Leiming Liu, Zhenyu Ju, Xian Wang, Hongchuan Jin, Lifeng Feng
Summary: High expression of WIP1 is associated with poor prognosis in patients with HCC. Inhibition of WIP1 and PARP induces synthetic lethality in HCC by augmenting DNA damage.
CELL COMMUNICATION AND SIGNALING
(2022)
Article
Cell Biology
Jiyeon Leem, Guang-Yu Bai, Jeong Su Oh
Summary: Maintaining genome integrity in germ cells is crucial for successful fertilization and embryo development. This study showed that inhibiting WIP1 activity enhances zygotic repair of paternal DNA damage, improving the development and genome activation in zygotes.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Biology
Iraia Garcia-Santisteban, Alba Llopis, Lenno Krenning, Jon Vallejo-Rodriguez, Bram van den Broek, Ana M. Zubiaga, Rene H. Medema
Summary: ATM becomes dispensable for G1 checkpoint maintenance as early as 1 hour after DSB induction, while CHK2 kinase activity is necessary to maintain G1 arrest independently of other proteins, suggesting that the G1 arrest is sustained in a lesion-independent manner.
Article
Oncology
Zhili Xia, Minzhen Li, Meng Hu, Yanyan Lin, Lawrence Lawer Atteh, Wenkang Fu, Long Gao, Mingzhen Bai, Chongfei Huang, Ping Yue, Yu Liu, Wenbo Meng
Summary: This study reveals the mechanism by which CB induces apoptosis of ICC cells through activating the ATM/CHK2/p53 signaling pathway and initiating DNA damage. This finding suggests that CB may serve as a potential chemotherapeutic drug candidate for ICC treatment.
FRONTIERS IN ONCOLOGY
(2022)
Article
Medicine, Research & Experimental
Qin Zhang, Lujie Yang, Han Gao, Xunjie Kuang, He Xiao, Chen Yang, Yi Cheng, Lei Zhang, Xin Guo, Yong Zhong, Mengxia Li
Summary: APE1 is upregulated in cervical tumor tissue and promotes radio-resistance. It activates non-homologous end joining (NHEJ) repair and plays a role in temporal formation and repair of DSBs. APE1 deficiency leads to DSB accumulation at a late phase following oxidative stress.
JOURNAL OF TRANSLATIONAL MEDICINE
(2023)
Article
Cell Biology
Vera Chesnokova, Svetlana Zonis, Athanasia Apostolou, Hannah Q. Estrada, Simon Knott, Kolja Wawrowsky, Kathrin Michelsen, Anat Ben-Shlomo, Robert Barrett, Vera Gorbunova, Katia Karalis, Shlomo Melmed, Kolja Wawrowsky, Kathrin Michelsen, Anat Ben-Shlomo, Robert Barrett, Vera Gorbunova, Katia Karalis, Shlomo Melmed
Summary: The study found that as individuals age, the level of non-pituitary growth hormone (npGH) in the body increases, leading to DNA damage accumulation. npGH can suppress p53 and weaken DNA repair response, accelerating DNA damage. Inhibiting npGH signaling could be a potential anti-aging therapy strategy.
Article
Genetics & Heredity
Yuichi Nishiyama, Akinori Morita, Shogo Tatsuta, Misaki Kanamaru, Masahiro Sakaue, Kenta Ueda, Manami Shono, Rie Fujita, Bing Wang, Yoshio Hosoi, Shin Aoki, Takeshi Sugai
Summary: Isorhamnetin has been found to possess radioprotective effects by enhancing the ATM-dependent DNA repair process, which may be associated with its suppressive effect against gastrointestinal syndrome.
Review
Genetics & Heredity
Hartwig Visser, Adam D. Thomas
Summary: The DNA damage response plays a crucial role in determining cell fate, with miRNAs potentially influencing cell fate by regulating key DDR proteins. While miRNAs are dysregulated in cancerous tissues, further research is needed to establish their functional association in this context.
Article
Biochemistry & Molecular Biology
Sara Giovannini, Marie-Christine Weller, Hana Hanzlikova, Tetsuya Shiota, Shunichi Takeda, Josef Jiricny
NUCLEIC ACIDS RESEARCH
(2020)
Article
Biochemistry & Molecular Biology
Ilona Kalasova, Richard Hailstone, Janin Bublitz, Jovel Bogantes, Winfried Hofmann, Alejandro Leal, Hana Hanzlikova, Keith W. Caldecott
NUCLEIC ACIDS RESEARCH
(2020)
Review
Cell Biology
Lenka Stolarova, Petra Kleiblova, Marketa Janatova, Jana Soukupova, Petra Zemankova, Libor Macurek, Zdenek Kleibl
Article
Biology
Helena Silva Cascales, Kamila Burdova, Anna Middleton, Vladislav Kuzin, Erik Mullers, Henriette Stoy, Laura Baranello, Libor Macurek, Arne Lindqvist
Summary: Cyclin A2 plays a key role in regulating the cell cycle and activating mitotic kinases. A change in localization of Cyclin A2 from nuclear to both nuclear and cytoplasmic at the S/G2 border is associated with its ability to activate PLK1 through phosphorylation of Bora. Cytoplasmic presence of Cyclin A2 functions as a trigger for mitotic kinase activation at the S/G2 transition.
LIFE SCIENCE ALLIANCE
(2021)
Article
Biochemistry & Molecular Biology
Emilia Komulainen, Jack Badman, Stephanie Rey, Stuart Rulten, Limei Ju, Kate Fennell, Ilona Kalasova, Kristyna Ilievova, Peter J. McKinnon, Hana Hanzlikova, Kevin Staras, Keith W. Caldecott
Summary: The study demonstrates that high activity of DNA strand break sensor protein Parp1 in mice with Xrcc1 deletion can result in lethal seizures, which can be prevented and lifespan extended by inhibiting or deleting Parp1. This highlights PARP inhibition as a potential therapeutic approach for hereditary neurological diseases.
Article
Biochemistry & Molecular Biology
Radka Storchova, Kamila Burdova, Matous Palek, Rene H. Medema, Libor Macurek
Summary: Upon exposure to genotoxic stress, cells activate DNA damage response (DDR) to coordinate DNA repair and temporarily arrest cell cycle progression. WIP1 protein plays a crucial role in controlling DDR and aiding cell recovery by counteracting the function of p53.
Article
Multidisciplinary Sciences
Wei Wu, Sarah E. Hill, William J. Nathan, Jacob Paiano, Elsa Callen, Dongpeng Wang, Kenta Shinoda, Niek van Wietmarschen, Jennifer M. Colon-Mercado, Dali Zong, Raffaella De Pace, Han-Yu Shih, Steve Coon, Maia Parsadanian, Raphael Pavani, Hana Hanzlikova, Solji Park, Seol Kyoung Jung, Peter J. McHugh, Andres Canela, Chongyi Chen, Rafael Casellas, Keith W. Caldecott, Michael E. Ward, Andre Nussenzweig
Summary: Defects in DNA repair can lead to neurodevelopmental and neurodegenerative diseases, particularly in long-lived post-mitotic neurons. Neurons accumulate unexpectedly high levels of DNA single-strand breaks at specific sites within the genome, which are repaired by PARP1 and XRCC1-dependent mechanisms. Deficiencies in XRCC1-dependent repair in neurons can lead to increased DNA repair synthesis at neuronal enhancers, while defects in long-patch repair reduce synthesis, potentially contributing to neurodegenerative phenotypes in patients.
Article
Biochemistry & Molecular Biology
Cecilia Aquino Perez, Monika Burocziova, Gabriela Jenikova, Libor Macurek
Summary: Cell cycle progression is regulated by cyclin-dependent kinases, which control gene expression, mitotic spindle coordination, and cell division. Through transcriptomic analysis, the study identified FAM110A as a protein highly expressed in G2 cells, contributing to chromosomal alignment and spindle positioning by interacting with CK1. The phosphorylation of FAM110A by CK1 during mitosis plays a crucial role in regulating these processes and promoting proper mitotic progression.
Article
Biochemistry & Molecular Biology
Annie A. Demin, Kouji Hirota, Masataka Tsuda, Marek Adamowicz, Richard Hailstone, Jan Brazina, William Gittens, Ilona Kalasova, Zhengping Shao, Shan Zha, Hiroyuki Sasanuma, Hana Hanzlikova, Shunichi Takeda, Keith W. Caldecott
Summary: PARPs and XRCC1 accelerate mammalian DNA base excision repair (BER), where XRCC1 prevents excessive PARP1 engagement during BER and traps PARP1 on BER intermediates. Excessive PARP1 engagement poses a threat to genome integrity, while XRCC1 acts as an anti-trapper preventing toxic PARP1 activity. Deletion of PARP1 rescues BER and resistance to base damage in XRCC1-deficient cells.
Article
Cell Biology
Marek Adamowicz, Richard Hailstone, Annie A. Demin, Emilia Komulainen, Hana Hanzlikova, Jan Brazina, Amit Gautam, Sophie E. Wells, Keith W. Caldecott
Summary: Toxic PARP1 activity induced by mutations in XRCC1 impairs global transcription recovery during DNA base excision repair by promoting aberrant recruitment and activity of the ubiquitin protease USP3. Inhibition or deletion of PARP1 or USP3 restores transcriptional recovery in XRCC1-deficient cells, suggesting them as potential therapeutic targets in neurological disease.
NATURE CELL BIOLOGY
(2021)
Article
Cell Biology
Anastasiya Klebanovych, Stanislav Vinopal, Eduarda Draberova, Vladimira Sladkova, Tetyana Sulimenko, Vadym Sulimenko, Vera Vosecka, Libor Macurek, Agustin Legido, Pavel Draber
Summary: ER distribution relies on microtubules, and disruption of ER homeostasis activates the unfolded protein response, leading to ER remodeling. UFL1 and C53 interact with gamma-tubulin ring complex proteins and regulate microtubule nucleation in response to ER stress. These findings reveal a novel mechanism for alleviating ER stress through stimulation of centrosomal microtubule nucleation.
Article
Biochemistry & Molecular Biology
Alina Vaitsiankova, Kamila Burdova, Margarita Sobol, Amit Gautam, Oldrich Benada, Hana Hanzlikova, Keith W. Caldecott
Summary: PARP inhibitors hinder the maturation of nascent DNA strands during DNA replication, particularly unligated Okazaki fragments and other discontinuities, resulting in cytotoxic effects. The activation of PARP1 is elevated in cells lacking the FEN1 nuclease, suggesting its involvement in the detection and processing of these DNA replication intermediates. PARP inhibitors disrupt the integrity of nascent DNA strands in both normal and FEN1(-/-) cells, leading to the formation of single-strand nicks or gaps. These findings highlight the importance of unligated Okazaki fragments and other discontinuities in the cytotoxicity of PARP inhibitors.
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Zuzana Cihlarova, Jan Kubovciak, Margarita Sobol, Katerina Krejcikova, Jana Sachova, Michal Kolar, David Stanek, Cyril Barinka, Grace Yoon, Keith W. Caldecott, Hana Hanzlikova
Summary: Mutations in BRAT1 are associated with neurodevelopmental delay and neurodegeneration. This study reveals that BRAT1 is a component of Integrator and plays a crucial role in the processing of specific RNAs. The authors also demonstrate that patient-derived cells with BRAT1 mutations show reduced levels of the Integrator catalytic subunit and impaired RNA processing.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Radka Storchova, Matous Palek, Natalie Palkova, Pavel Veverka, Tomas Brom, Ctirad Hofr, Libor Macurek
Summary: Protein phosphatase magnesium-dependent 1 delta (PPM1D) terminates the cell cycle checkpoint by dephosphorylating the tumour suppressor protein p53. PPM1D also targets substrates at chromatin and contributes to the control of DNA damage response and DNA repair. The interaction between PPM1D and the shelterin complex at telomeres, as well as the role of TRF2 phosphorylation in regulating DNA repair, were identified in this study.
NUCLEIC ACIDS RESEARCH
(2023)
Review
Biochemistry & Molecular Biology
Barbora Otahalova, Zuzana Volkova, Jana Soukupova, Petra Kleiblova, Marketa Janatova, Michal Vocka, Libor Macurek, Zdenek Kleibl
Summary: The MRE11, RAD50, and NBN genes encode for the MRN protein complex responsible for DNA repair and coordinating with cell cycle checkpoint arrest. Mutations in these genes can cause autosomal recessive syndromes and increase the risk of various cancers. Somatic alterations in these genes may serve as predictive and prognostic biomarkers in cancer patients. However, interpreting alterations in these genes is challenging due to the complexity of their function in DNA damage response.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)