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.
Article
Oncology
Shunsuke Hanaki, Makoto Habara, Takahiro Masaki, Keisuke Maeda, Yuki Sato, Makoto Nakanishi, Midori Shimada
Summary: The study uncovered that NIPP1 functions as a modulator of E2F1 target genes by linking PKA and PP1γ during DNA damage, playing a crucial role in cell proliferation.
Review
Biochemistry & Molecular Biology
Vladimir Baran, Alexandra Mayer
Summary: After fertilization, the remodeling of the oocyte and sperm genome is crucial for the successful initiation of mitotic activity in the fertilized oocyte and subsequent proliferation of the early embryo. The specific nature of gene totipotency in early cleavage embryos leads to differences in cell cycle control mechanisms compared to somatic cells. This review focuses on the Chk1 kinase as an important factor in monitoring DNA integrity during early embryogenesis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Yandong Yin, Wei Ting, Chelsea Lee, Dipika Gupta, Tony T. Huang, Mauro Modesti, Eli Rothenberg, Yandong Yin, Wei Ting Chelsea Lee
Summary: A study conducted using advanced microscopy techniques discovered that ATR plays a crucial role in monitoring and regulating the amounts of RPA at forks during unperturbed replication and replication stress. Replication stress amplifies the basal activity of ATR by increasing the ATR-RPA interaction and enrichment of ATR at specific sites, ultimately enhancing its activation and replication stress response.
Review
Oncology
Congqi Shi, Kaiyu Qin, Anqi Lin, Aimin Jiang, Quan Cheng, Zaoqu Liu, Jian Zhang, Peng Luo
Summary: This study summarizes currently identified and promising biomarkers for predicting the response of oncology patients to immune checkpoint inhibitors, and explores the mechanism of combination therapy with immune checkpoint inhibitors and DNA damage repair inhibitors.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Benjamin R. Stromberg, Mayank Singh, Adrian E. Torres, Amy C. Burrows, Debjani Pal, Christine Insinna, Yosup Rhee, Andrew S. Dickson, Christopher J. Westlake, Matthew K. Summers
Summary: The deubiquitinating enzyme USP37 is required beyond S-phase entry to promote the efficiency and fidelity of replication. Depletion of USP37 leads to increased replication stress and DNA damage, reduced cellular proliferation, and increased sensitivity to agents that induce replication stress. USP37 stabilizes checkpoint kinase 1 to ensure proper function and plays a crucial role in regulating cell proliferation and genome stability.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Cell Biology
Kyung Yong Lee, Anindya Dutta
Summary: The cell-cycle phase plays a crucial role in determining repair pathway choice at DNA double-strand breaks, with Chk1 promoting non-homologous end joining (NHEJ) repair in the G1 phase. ASF1A, a histone chaperone, also promotes NHEJ independently of its chaperone activity. Chk1 phosphorylates ASF1A at Ser-166 in G1, enhancing its interaction with the repair protein MDC1 and promoting NHEJ repair.
Review
Biochemistry & Molecular Biology
Pin Zhao, Samiullah Malik
Summary: This review describes how phosphorylation affects the transcription activity and other functions of DNA/histone modifying enzymes. Although the phosphorylated sites of these enzymes have been classified and partially explained, further research is still needed to determine their relationship with disease-associated transcriptional regulation.
CELL AND BIOSCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Sophie L. Cooke, Barbara L. Soares, Carolin A. Muller, Conrad A. Nieduszynski, Francisco M. Bastos de Oliveira, Robertus A. M. de Bruin
Summary: Saccharomyces cerevisiae maintains gene expression homeostasis through an active mechanism involving Tos4 and the Rpd3L HDAC complex, independent of H3K56 acetylation.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Diana Ainembabazi, Xinran Geng, Navnath S. Gavande, John J. Turchi, Youwei Zhang
Summary: Cardiac glycosides have been found to have anticancer activity in addition to their original use in treating heart diseases. This study successfully synthesized cardiac glycoside derivatives and identified structure-activity relationships that contribute to their anticancer activity. This finding is important for further optimization of cancer therapeutics.
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
Oncology
Fiifi Neizer-Ashun, Resham Bhattacharya
Summary: The DNA damage response relies on CHK1 kinase for maintaining genomic integrity, involving in processes such as DNA replication and mitotic progression. While CHK1 has potential in cancer therapy, it has yet to be fully realized clinically.
Article
Medicine, Research & Experimental
Liwei An, Zhifa Cao, Pingping Nie, Hui Zhang, Zhenzhu Tong, Fan Chen, Yang Tang, Yi Han, Wenjia Wang, Zhangting Zhao, Qingya Zhao, Yuqin Yang, Yuanzhi Xu, Gemin Fang, Lei Shi, Huixiong Xu, Haiqing Ma, Shi Jiao, Zhaocai Zhou
Summary: We identified the Hippo-STRIPAK complex as a crucial regulator of DNA double-stranded break (DSB) repair and genomic stability. Inhibition of STRIPAK-mediated MST1/2 activation increased the DSB repair capacity of cancer cells and conferred resistance to radio- and chemotherapy and PARP inhibition. Furthermore, targeting the STRIPAK assembly effectively restored the kinase activity of MST1/2 and resensitized cancer cells to PARP inhibitors. Our findings suggest a previously unrecognized role for STRIPAK in modulating DSB repair and provide translational implications for a new type of synthetic lethality anticancer therapy by cotargeting STRIPAK and PARP.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
Review
Genetics & Heredity
Onyekachi E. Ononye, Michael Downey
Summary: This review summarizes the types and functions of posttranslational modifications that regulate Gcn5 in both yeast and human cells. Common themes, unanswered questions, and strategies for future research are also outlined.
Article
Multidisciplinary Sciences
Devashish Dwivedi, Daniela Harry, Patrick Meraldi
Summary: This study reveals that mild replication stress leads to premature centriole disengagement while delaying mitotic onset. This is caused by sub-critical Plk1 kinase activity, enabling centrosome cycling but impeding rapid mitotic entry.
NATURE COMMUNICATIONS
(2023)