Review
Biochemistry & Molecular Biology
Lindsey Carlsen, Wafik S. El-Deiry
Summary: The TP53 gene, encoding the tumor suppressor protein p53, is mutated in around 50% of cancers. After DNA damage, p53 acts as a transcription factor to activate target genes for cell fates such as apoptosis, cell cycle arrest, and DNA repair. The complex regulatory network controlling target gene selection by p53 varies across contexts such as treatment type, cell type, and tissue type.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Mi Ae Kang, Jong-Soo Lee
Summary: CTCF, a highly conserved multifunctional DNA-binding protein with 11 zinc fingers, plays crucial roles in diverse genomic processes such as transcriptional regulation, insulation, genome imprinting, and maintenance of genome organization. Recent findings reveal that CTCF is involved in DNA double-strand break (DSB) repair through homologous recombination (HR), facilitating accurate restoration of broken DNA sequences. Understanding the functional crosstalks between CTCF and other HR factors may shed light on the molecular basis of various human diseases and the diverse functions of CTCF in genome biology.
Article
Cell Biology
Akshay Narkar, Blake A. Johnson, Pandurang Bharne, Jin Zhu, Veena Padmanaban, Debojyoti Biswas, Andrew Fraser, Pablo A. Iglesias, Andrew J. Ewald, Rong Li
Summary: Studies suggest that p53 may not serve as a universal surveillance factor restricting the proliferation of aneuploid cells, but instead play a role in ensuring faithful chromosome transmission likely by preventing polyploidization and influencing spindle mechanics, both directly or indirectly.
Article
Biology
Kerrie-Ann Mcmahon, David A. Stroud, Yann Gambin, Vikas Tillu, Michele Bastiani, Emma Sierecki, Mark E. Polinkovsky, Thomas E. Hall, Guillermo A. Gomez, Yeping Wu, Marie-Odile Parat, Nick Martel, Harriet P. Lo, Kum Kum Khanna, Kirill Alexandrov, Roger Daly, Alpha Yap, Michael T. Ryan, Robert G. Parton
Summary: Cavin3 plays a key role in DNA repair and interacts directly with BRCA1. Loss of cavin3 can increase the sensitivity of tumor cells to UV-induced apoptosis, while also affecting DNA repair and cell survival.
Review
Biochemistry & Molecular Biology
Jac A. Nickoloff, Aruna S. Jaiswal, Neelam Sharma, Elizabeth A. Williamson, Manh T. Tran, Dominic Arris, Ming Yang, Robert Hromas
Summary: Replicative DNA polymerases are obstructed by various DNA damage, leading to DNA replication stress that threatens genome stability. Cellular responses to replication stress include cell cycle arrest, replication fork collapse, DNA repair induction, and programmed cell death. Nucleases play critical roles in these responses, promoting repair and restart of stressed replication forks. Understanding biological responses to genome-wide replication stress can inform novel cancer treatment strategies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
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
Pharmacology & Pharmacy
Yanting Yang, Xiuhong Zhu, Guohua Yu, Jinbo Ma
Summary: This study demonstrates that Pyxinol can mitigate cisplatin-induced renal injury by attenuating DNA damage response and tubular cell apoptosis. Furthermore, Pyxinol can enhance the in vivo anti-tumor efficacy of cisplatin against xenograft tumors in nude mice. The combination of Pyxinol with cisplatin may represent a beneficial adjunct therapy for cisplatin-based chemotherapeutic regimens in the clinic.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Ting-Yu Chen, Bu-Miin Huang, Tang K. Tang, Yu-Ying Chao, Xiao-Yi Xiao, Pei-Rong Lee, Li-Yun Yang, Chia-Yih Wang
Summary: The DNA-PK-p53 cascade induces primary cilia formation under genotoxic stress, contributing to the DNA damage response, while lack of this pathway decreases genotoxic stress-induced ciliogenesis. Besides, ciliogenesis is regulated not only by DNA-PK, but also by autophagy.
CELL DEATH AND DIFFERENTIATION
(2021)
Review
Biochemistry & Molecular Biology
Beth Wilkinson, Mark A. A. Hill, Jason L. L. Parsons
Summary: Radiotherapy using ionising radiation is a common treatment for many cancers, as it damages the DNA of cancer cells. Complex DNA damage (CDD), which is difficult to repair, is a key contributor to the cell-killing effects of radiotherapy. The level and complexity of CDD increase with higher ionisation density of the radiation. Detecting and measuring IR-induced CDD in cells and tissues poses challenges, and there are uncertainties regarding the specific DNA repair mechanisms involved. However, advancements are being made in these areas to improve understanding of cellular responses to CDD and explore targeted therapies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cell Biology
Lin Tze Tung, HanChen Wang, Jad I. Belle, Jessica C. Petrov, David Langlais, Anastasia Nijnik
Summary: The study examined the in vivo transcriptional response of hematopoietic stem and progenitor cells to genotoxic stress, identifying p53-independent induction of inflammatory transcriptional signatures and multiple novel p53-target genes. Additionally, the study demonstrated the significant role of P2X7 in hematopoietic response to acute genotoxic stress.
CELL DEATH & DISEASE
(2021)
Article
Cell Biology
Dong Li, Ying Ge, Ze Zhao, Rui Zhu, Xiang Wang, Xiaolin Bi
Summary: The study analyzed the expression profiles of miRNAs and piRNAs in Drosophila during development and DNA damage response, revealing dynamic expression patterns and the key roles of E2f1 and p53 in regulating small ncRNAs. E2f1 may play a major role in modulating miRNAs during development and after X-ray irradiation, showcasing new insights into small ncRNA biology.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Lindsey Carlsen, Shengliang Zhang, Xiaobing Tian, Arielle De La Cruz, Andrew George, Taylor E. E. Arnoff, Wafik S. S. El-Deiry
Summary: p53 is a transcription factor that regulates tumor suppressor genes. Mutations in p53 are common in human cancers and can impact immune responses. p53 can induce different cellular responses such as apoptosis, cell cycle arrest, and DNA damage repair by regulating target genes.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Marina Maria Bellet, Claudia Stincardini, Claudio Costantini, Marco Gargaro, Stefania Pieroni, Marilena Castelli, Danilo Piobbico, Paolo Sassone-Corsi, Maria Agnese Della-Fazia, Luigina Romani, Giuseppe Servillo
Summary: The circadian clock regulates fundamental physiological processes and can impact the response to anticancer treatments, but the molecular mechanisms linking circadian rhythms to anticancer actions are still poorly understood, limiting the application of chronotherapy in clinical practice.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Oncology
Meiling Zhou, Liang Xiao, Jing Jin, Yin Wang, Peiyu Guo, Jinhua Luo, Magdalena Skonieczna, Ruixue Huang
Summary: This study revealed the epigenetic mechanisms underlying Nano-ZnO-induced DNA damage and EMT. The effect of Nano-ZnO-induced DNA damage through the p53/circRNA_0085439/Ku70 pathway likely contributes to Nano-ZnO-induced cell cytotoxicity and apoptosis. These findings provide important information to further elucidate the molecular mechanisms of Nano-ZnO-induced cytotoxicity and genotoxicity.
CANCER NANOTECHNOLOGY
(2023)
Article
Oncology
Domenica Berardi, Yasmin Hunter, Lisa van den Driest, Gillian Farrell, Nicholas J. W. Rattray, Zahra Rattray
Summary: This study comprehensively analyzed the DNA damage repair and cellular metabolism of breast cancer cell lines in response to olaparib treatment using molecular biology and metabolomics approaches. The findings revealed dysregulation of amino acid metabolism and metabolic reprogramming as common features in all breast cancer cell lines, some of which were consistent with clinical breast cancer tumor analysis.
