Article
Biochemistry & Molecular Biology
Xiaotong Zhao, Manman Zhang, Jinhan Wang, Kaihua Ji, Yan Wang, Xiaohui Sun, Chang Xu, Qin Wang, Ningning He, Huijuan Song, Liqing Du, Feng Wang, Hao Huang, Yang Liu, Qiang Liu
Summary: The risk of cancer increases with age, and radiotherapy often causes intestinal damage. NRF2, a key protective factor, decreases with aging. NRF2 deficiency worsens cellular DNA damage and intestinal pathological damage. SIRT6 or SIRT7 overexpression improves cell proliferation and protects against radiation damage in NRF2 KO cells. Supplementation of NMN increases SIRT6 and SIRT7 levels, reduces cellular ROS, and ameliorates DNA damage in NRF2 KO cells. Long-term oral NMN administration attenuates radiation-induced jejunum injury, increases the number of intestinal stem cells, and promotes intestinal proliferation in NRF2-/- mice.
FREE RADICAL BIOLOGY AND MEDICINE
(2022)
Article
Oncology
T. S. Freire, M. P. Mori, J. N. F. A. Miranda, L. Y. M. Muta, F. T. Machado, N. C. Moreno, N. C. Souza-Pinto
Summary: XPC deficiency is linked to mitochondrial dysfunction and increased p53 expression, while treatment with antioxidants can help restore cellular balance.
Article
Oncology
Cholpon S. Djuzenova, Thomas Fischer, Astrid Katzer, Dmitri Sisario, Tessa Korsa, Gudrun Steussloff, Vladimir L. Sukhorukov, Michael Flentje
Summary: In this study, the triple-target inhibitor PI-103 sensitized MO59K cells to radiation, but unexpectedly caused radioresistance in the MO59J line. The difference is likely due to low expression of the DNA-PK substrate p53 in MO59J cells, which was further reduced by PI-103. This led to decreased apoptosis in comparison to drug-free MO59J cells and enhanced survival through partially abolished cell-cycle arrest. The findings suggest that the lack of DNA-PK-dependent NHEJ in MO59J line might be compensated by DNA-PK independent DSB repair via an unknown mechanism.
Editorial Material
Oncology
Antoine Italiano
Summary: In a phase I trial, Yap and colleagues found that the ATR inhibitor BAY 1895344 is safe and induces durable responses in ATM-deficient tumors. This opens up possibilities for innovative combination regimens targeting DNA damage response defects in cancer.
Article
Biochemistry & Molecular Biology
Jian-Lei Zhao, Jun Yang, Ke Li, Yang Chen, Mei Tang, Hui -Li Zhu, Chun-Lai Nie, Zhu Yuan, Xin-Yu Zhao
Summary: Targeting replication stress response is a promising therapeutic strategy for breast tumors, and combination therapy of ATR inhibitor and cisplatin may offer potential benefits.
CHEMICO-BIOLOGICAL INTERACTIONS
(2023)
Article
Environmental Sciences
Yan Jin, Yiting Li, Shiyi He, Yijun Ge, Yun Zhao, Ke Zhu, Andong He, Siyu Li, Siyu Yan, Chao Cao
Summary: PM2.5 induces airway inflammation and DNA damage, and the ATM gene plays a role in promoting this inflammation.
ENVIRONMENTAL TOXICOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Bhanu Priya, Gurudutt Dubey, Sivapriya Kirubakaran
Summary: This study investigates the therapeutic potential of SPK98 in P53- and ATM-deficient cancer cells. The results show that SPK98 selectively sensitizes these cells and induces DNA double-strand breaks, making it a promising therapeutic molecule for P53- or ATM-deficient malignancies.
Review
Cell Biology
Maria Gonzalez-Amor, Beatriz Dorado, Vicente Andres
Summary: Population aging and age-related cardiovascular disease (CVD) are widespread and burdensome worldwide. Cellular stress responses play a crucial role in the complex regulation and interaction between aging and CVD. The ubiquitin-like protein ISG15 and its pathway have been found to have implications in age-related telomere shortening, genomic instability, DNA damage accumulation, as well as in major CVD risk factors prevalent in the elderly population such as hypertension, diabetes, and obesity.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Article
Cell Biology
Chao Mei, Ze-En Sun, Li-Ming Tan, Jian-Ping Gong, Xi Li, Zhao-Qian Liu
Summary: Our study demonstrates that eIF3a continuously activates the ATM/ATR signaling pathway by inhibiting the translation of PPP2R5A, leading to chronic phosphorylation and activation of ATM/ATR. This impairs DNA repair and enhances the sensitivity to irinotecan.
CELL PROLIFERATION
(2022)
Review
Cell Biology
Davide Cinat, Robert P. Coppes, Lara Barazzuol
Summary: This review discusses how DNA damage affects the maintenance and function of stem cells in adult tissues and neoplasms, leading to inflammatory responses and changes in the microenvironment. DNA damage can induce cell senescence, increase pro-inflammatory factors release, and modulate immune responses, potentially impacting tissue homeostasis and cancer development. Understanding the DNA damage-induced immunomodulatory responses on stem cell microenvironment may provide insights into age-related diseases and cancer, offering novel treatment strategies.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Oncology
Jiajing Niu, Jiamei Wang, Qi Zhang, Zhihua Zou, Yushuang Ding
Summary: The study revealed that sublethal doses of cinobufagin suppressed the viability of cancer cells by inducing oxidative stress, leading to DNA damage and cell cycle regulation that ultimately resulted in the induction of apoptosis.
CANCER CELL INTERNATIONAL
(2021)
Article
Multidisciplinary Sciences
Ke Shi, Nicholas H. Moeller, Surajit Banerjee, Jennifer L. McCann, Michael A. Carpenter, Lulu Yin, Ramkumar Moorthy, Kayo Orellana, Daniel A. Harki, Reuben S. Harris, Hideki Aihara
Summary: EndoQ repairs DNA mutations caused by deamination through cleaving the DNA backbone with selectivity depending on DNA distortion and hydrogen bonds with deaminated bases. The enzyme clamps down on a sharply bent DNA substrate with a zinc-binding and C-terminal helical domain swing motion, shaping a deep active-site pocket for accommodating the extruded deaminated base.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Multidisciplinary Sciences
Nichole Owen, Irina G. Minko, Samantha A. Moellmer, Sydney K. Cammann, R. Stephen Lloyd, Amanda K. McCullough
Summary: Human clinical trials suggest that inhibition of enzymes in the DNA base excision repair (BER) pathway, such as PARP1 and APE1, can be useful in anticancer strategies when combined with certain DNA-damaging agents. Specifically, in acute myeloid leukemia (AML), AML cell lines deficient in OGG1 have enhanced sensitivity to cytarabine (Ara-C) treatment. This enhanced cytotoxicity is likely due to the insertion of Ara-C opposite unrepaired 8-oxo-dG in OGG1-deficient AML cells.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Review
Cell Biology
John M. M. Danforth, Luc Provencher, Aaron A. A. Goodarzi
Summary: Exposure to environmental ionizing radiation, particularly high-LET radiation, can induce clustered DNA damage that is challenging to repair. Understanding the role of chromatin in the repair process is essential for assessing the effects of radiation exposure.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Samuel B. Bader, Tiffany S. Ma, Charlotte J. Simpson, Jiachen Liang, Sakura Eri B. Maezono, Monica M. Olcina, Francesca M. Buffa, Ester M. Hammond
Summary: This study demonstrates that fluctuating hypoxic conditions inducing replication catastrophe lead to increased expression and activity of APOBEC3B, contributing to the accumulation of APOBEC-mediated mutations. In contrast, stable hypoxic conditions do not significantly impact APOBEC3B. The number of APOBEC-mediated mutations in patient tumors is closely correlated with a hypoxia signature, indicating that hypoxia-induced replication catastrophe drives genomic instability in tumors through increasing the activity of APOBEC3B.
NUCLEIC ACIDS RESEARCH
(2021)