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.
Review
Oncology
Rick A. C. M. Boonen, Maaike P. G. Vreeswijk, Haico van Attikum
Summary: Protein-truncating variants in the breast cancer susceptibility gene CHEK2 are associated with an increased risk of breast cancer, while the risk associated with missense variants of uncertain significance is often unclear. Functional assays have been conducted to determine the impact of missense variants on CHK2 protein function, consistently revealing an association between impaired function and increased breast cancer risk. These findings indicate the urgency of expanding the functional characterization of CHEK2 missense variants to further understand the associated cancer risk.
Article
Multidisciplinary Sciences
Leilei Qi, Reka Chakravarthy, Monica M. Li, Chu-Xia Deng, Rong Li, Yanfen Hu
Summary: BRCA1-S1152 is part of a feedback loop that sustains ATM activity, and its mutation leads to deficient ATM activation and end resection in the HR repair pathway. Surprisingly, the mutation of mouse ATM-S1987 maintains damage-induced ATM kinase activation, suggesting a species-specific function in the ATM feedback loop.
Article
Biochemistry & Molecular Biology
Zhongyan Li, Shangfu Li, Mengqi Luo, Jhih-Hua Jhong, Wenshuo Li, Lantian Yao, Yuxuan Pang, Zhuo Wang, Rulan Wang, Renfei Ma, Jinhan Yu, Yuqi Huang, Xiaoning Zhu, Qifan Cheng, Hexiang Feng, Jiahong Zhang, Chunxuan Wang, Justin Bo-Kai Hsu, Wen-Chi Chang, Feng-Xiang Wei, Hsien-Da Huang, Tzong-Yi Lee
Summary: This paper presents an update of dbPTM with over 2,777,000 PTM substrate sites, of which more than 2,235,000 entries are experimentally verified. The update includes 42 new modification types and collates regulatory information from databases into a protein-protein interaction network, shedding light on the association between PTMs and molecular functions.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Cell Biology
Yang Wang, Tianyu Yu, Yi Han, Yazhi He, Yiran Song, Leiming Guo, Liwei An, Chunying Yang, Feng Wang
Summary: This study reveals the key regulatory role of Mad2 phosphorylation in checkpoint defects and DNA damage repair in ATM-deficient cells. ATM negatively regulates the phosphorylation of Mad2, causing decreased DNA damage repair capacity and resistance to cancer cell radiotherapy.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Gastroenterology & Hepatology
Laura Elisa Buitrago-Molina, Silke Marhenke, Diana Becker, Robert Geffers, Timo Itzel, Andreas Teufel, Hartmut Jaeschke, Andre Lechel, Kristian Unger, Jovana Markovic, Amar Deep Sharma, Jens U. Marquardt, Michael Saborowski, Anna Saborowski, Arndt Vogel
Summary: The study found that loss of p53 in a model of metabolic liver injury impairs the oxidative stress response, aggravates liver damage, and shows a complex interdependency between p21 and p53.
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Ho Tsoi, Wai-Chung Tsang, Ellen P. S. Man, Man-Hong Leung, Chan-Ping You, Sum-Yin Chan, Wing-Lok Chan, Ui-Soon Khoo
Summary: This study reveals that tamoxifen treatment can enhance the expression of BQ in ER-positive breast cancer by activating the ATM/CHK2 axis. Targeting CHK2 is a promising approach to overcoming tamoxifen resistance in ER-positive breast cancer.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Medicine, General & Internal
Ryoko Horigome, Kenya Kamimura, Yusuke Niwa, Kohei Ogawa, Ken-Ichi Mizuno, Koichi Fujisawa, Naoki Yamamoto, Taro Takami, Tomoyuki Sugano, Akira Sakamaki, Hiroteru Kamimura, Masaaki Takamura, Shuji Terai
Summary: The DSS-induced colitis mouse model causes colon shortening and increased disease activity index, while also activating the Atm-Chk2 pathway and inducing cell apoptosis at the cellular level. Knockout mice lacking the Ccndbp1 gene exhibit better protection against DSS-induced colitis.
JOURNAL OF CLINICAL MEDICINE
(2022)
Article
Multidisciplinary Sciences
Luke A. Yates, Elias A. Tannous, R. Marc Morgan, Peter M. Burgers, Xiaodong Zhang
Summary: This study reveals the phosphorylation circuit that regulates checkpoint recruitment and function in response to DNA damage. The interaction between Ddc2 and RPA modulates the association between RPA and ssDNA, and phosphorylated Ddc2 enhances its recruitment to RPA-ssDNA, promoting DNA damage checkpoint signaling.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Medicine, General & Internal
Yusuke Niwa, Kenya Kamimura, Kohei Ogawa, Chiyumi Oda, Yuto Tanaka, Ryoko Horigome, Masato Ohtsuka, Hiromi Miura, Koichi Fujisawa, Naoki Yamamoto, Taro Takami, Shujiro Okuda, Masayoshi Ko, Takashi Owaki, Atsushi Kimura, Osamu Shibata, Shinichi Morita, Norihiro Sakai, Hiroyuki Abe, Takeshi Yokoo, Akira Sakamaki, Hiroteru Kamimura, Shuji Terai
Summary: This study focused on investigating the function of Cyclin D1 binding protein 1 (CCNDBP1) in the survival of cancer cells by rescuing them from DNA damage caused by chemotherapy. The research revealed that CCNDBP1, by inhibiting EZH2, contributes to the activation of the ATM-CHK2 pathway and alleviates DNA damage, leading to chemoresistance.
JOURNAL OF CLINICAL MEDICINE
(2022)
Article
Oncology
Nicola Lockwood, Silvia Martini, Ainara Lopez-Pardo, Katharina Deiss, Hendrika A. Segeren, Robert K. Semple, Ian Collins, Dimitra Repana, Mathias Cobbaut, Tanya Soliman, Francesca Ciccarelli, Peter J. Parker
Summary: G2 arrest is crucial for the faithful segregation of sister chromatids, and the p53-p21 signaling pathway plays an essential role in cell lines, patient-derived cells, and colorectal cancer organoids. In arrest-defective hTERT-positive cells, the PKC epsilon failsafe mechanism is engaged. In ALT-dependent cancer cells, a distinct form of p53-independent G2 arrest is mediated by BLM and Chk1.
Review
Cell Biology
Stefano Sechi, Roberto Piergentili, Maria Grazia Giansanti
Summary: Cytokinesis, the final stage of cell division, plays a crucial role in normal development and preventing cancer. Kinase-mediated phosphorylation is a key process in regulating cytokinesis. While some kinases have well-established roles, others have been less studied but may uncover new pathways of cell division regulation.
Article
Cell Biology
Shuo Zhou, An Zhao, Yangyang Wu, Tingting Bao, Yuling Mi, Caiqiao Zhang
Summary: Aging in laying hens leads to increased follicular atresia and decreased fecundity, with FSH playing a crucial role in preventing reproductive aging. The study found that FSH can delay the progression of atretic small white follicles in hens by inhibiting DNA damage and promoting repair mechanisms, ultimately protecting granulosa cells from aging-related damage.
Article
Biochemistry & Molecular Biology
Ashley G. Boice, Karla E. Lopez, Raj K. Pandita, Melissa J. Parsons, Chloe Charendoff, Vijay Charaka, Alexandre F. Carisey, Tej K. Pandita, Lisa Bouchier-Hayes
Summary: The study demonstrates that caspase-2 is activated in dividing cells in G1 phase of the cell cycle and plays a crucial role in maintaining genomic stability by protecting cells from replication stress and promoting replication fork protection. These functions are independent of its pro-apoptotic role and involve regulating cell cycle and DNA repair events to prevent the accumulation of DNA damage.
Article
Biology
Erik Waskiewicz, Michalis Vasiliou, Isaac Corcoles-Saez, Rita S. Cha
Summary: Through data mining and functional genetic analysis, the study identified functionally important and evolutionarily conserved residues in ATM/ATR, shedding light on their diverse roles in enzyme functions. The findings suggest that loss of intrinsic kinase activity in ATM/ATR is infrequent in carcinogenesis.
COMMUNICATIONS BIOLOGY
(2021)