Review
Chemistry, Medicinal
Katharigatta N. N. Venugopala
Summary: Lung cancer is a frequently diagnosed cancer and a leading cause of death worldwide. Current treatment outcomes for small-cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) patients are unsatisfactory. DNA sequencing technologies have shown promise in studying tumor mutations. However, limited trials have been conducted for DDR inhibition in SCLC and NSCLC, and further exploration of combination therapies and targeting multiple pathways is needed. The review article discusses DNA repair pathways and inhibitors targeting proteins in the DDR machinery, such as ATR, DNA-PK, and PARP, as well as the current status and future perspectives of DDR inhibitors in clinical settings.
Article
Cell Biology
Matteo Cabrini, Marco Roncador, Alessandro Galbiati, Lina Cipolla, Antonio Maffia, Fabio Iannelli, Simone Sabbioneda, Fabrizio d'Adda di Fagagna, Sofia Francia
Summary: The DDR is a signaling cascade that recognizes DNA double-strand breaks and promotes their resolution via DNA repair pathways. DROSHA is recruited at DSBs by the MRN complex, directing DNA repair towards NHEJ. Inactivation of DROSHA reduces NHEJ and boosts HR frequency.
JOURNAL OF CELL SCIENCE
(2021)
Article
Cell Biology
Muddenahalli Srinivasa Sudhanva, Gurusamy Hariharasudhan, Semo Jun, Gwanwoo Seo, Radhakrishnan Kamalakannan, Hyun Hee Kim, Jung-Hee Lee
Summary: This study demonstrates that miR-145 suppresses DNA-PKcs expression, affecting DNA double-strand break repair and rendering cells sensitive to ionizing radiation. Additionally, miR-145 inhibition is associated with increased Akt1 phosphorylation and upregulation of DNA-PKcs in cancer cells.
Article
Biochemistry & Molecular Biology
Xile Pei, Emil Mladenov, Aashish Soni, Fanghua Li, Martin Stuschke, George Iliakis
Summary: The study investigates the role of PTEN in DNA double-strand break (DSB) repair. The loss of PTEN sensitizes cells to radiation by suppressing RAD51 expression and inhibiting homologous recombination, leading to an increase in error-prone single strand annealing.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Yi Wang, Yanjie Zhao, Weijun Su, Xiaojing Guo, Shuai Li
Summary: A CRISPR-Cas9 based luciferase turn-on system was developed as an NHEJ pathway reporter, with nucleotide substitution creating a silent bioluminescent signal in reporter cells. The system was validated using known chemical inhibitors of the NHEJ pathway, which significantly inhibited the bioluminescent signal generated by CRISPR-Cas9 targeting. The study demonstrated the potential for screening and discovery of NHEJ chemical inhibitors.
Article
Plant Sciences
Koppolu Raja Rajesh Kumar
Summary: The DNA-dependent protein kinase catalytic subunit (DNA-PKcs) encoded by the PRKDC gene is essential for repairing DNA double-strand breaks in humans. It also has additional roles in transcriptional regulation, telomere protection, chromosomal integrity, and cellular processes. Dysregulation of DNA-PKcs is commonly observed in cancers. Recent studies have found that DNA-PKcs is conserved in green plants but not in angiosperms or basal angiosperms. Challenges in detecting DNA-PKcs sequences in plants are attributed to its long polypeptide and gene length. Alignment of sequences between plants and humans suggests possible structural and functional conservation, highlighting the potential significance of DNA-PKcs in plant biology.
FRONTIERS IN PLANT SCIENCE
(2023)
Article
Biology
Simon Magin, Prabodha Kumar Meher, George Iliakis
Summary: Alt-EJ is a DNA repair pathway that can be utilized by vertebrate cells to repair DNA double-strand breaks, but its engagement is linked to genomic instability. Exposure to ionizing radiation and treatment with nucleoside analogs can sensitize cells to radiation by increasing alt-EJ engagement and suppressing homologous recombination. This pathway shift may reflect a compensatory response to HR suppression in S and G2 phase cells.
RADIATION RESEARCH
(2021)
Review
Oncology
Daniele Caracciolo, Caterina Riillo, Maria Teresa Di Martino, Pierosandro Tagliaferri, Pierfrancesco Tassone
Summary: Cancer onset and progression result in high levels of DNA damage, with error-prone DNA repair pathways promoting genomic instability that leads to the appearance of cancer hallmarks through progressive genetic aberrations in tumor cells. This provides a potential target for precision oncology through the inhibition of Alternative Non-Homologous End Joining (Alt-NHEJ) as a new cancer vulnerability.
Article
Biochemistry & Molecular Biology
Lisa Marie Krieger, Emil Mladenov, Aashish Soni, Marilen Demond, Martin Stuschke, George Iliakis
Summary: The decompaction of chromatin induced by hypotonic stress affects the processing and repair of DNA double-strand breaks (DSBs), leading to increased sensitivity of cells to ionizing radiation-induced damage and compromising genomic stability. This is achieved through suppression of homologous recombination (HR) and enhancement of error-prone processing by alternative end-joining (alt-EJ) and single-strand annealing (SSA).
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Emil Mladenov, Veronika Mladenova, Martin Stuschke, George Iliakis
Summary: Radiation therapy is an essential part of cancer management, utilizing different modalities of ionizing radiation to mitigate cancer progression. This article reviews the molecular mechanisms underlying the repair pathways involved in DNA damage caused by radiation therapy. It discusses factors and processes that influence the choice of repair pathways throughout the cell cycle and highlights the preference for homologous recombination at low radiation doses. The article also explores the molecular basis of transitions from high fidelity to error-prone repair pathways and analyzes the coordination and consequences of this transition on cell viability and genomic stability. Lastly, it discusses how these advances can contribute to the development of improved cancer treatment protocols in radiation therapy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Genetics & Heredity
Aditya Mojumdar, Nancy Adam, Jennifer A. Cobb
Summary: A DNA double strand break can be repaired by either non-homologous end-joining (NHEJ) or homologous recombination (HR). Nej1 is a key factor in NHEJ that inhibits resection and stimulates ligation. The C-terminal region of Nej1 plays a vital role in promoting NHEJ.
Article
Environmental Sciences
Eka Djatnika Nugraha, June Mellawati, Wahyudi, Chutima Kranrod, Makhsun, Hirofumi Tazoe, Haeranah Ahmad, Masahiro Hosoda, Naofumi Akata, Shinji Tokonami
Summary: The study in Mamuju, Indonesia, found high levels of natural radionuclides and heavy metals in the soil, indicating moderate contamination. The pollution indices and correlation analyses showed potential hazards to human health in Mamuju due to the presence of Pb and other heavy metals. Measures need to be taken to address and monitor the environmental pollution in Mamuju.
Article
Oncology
Zhipeng Du, Fangxiao Zhang, Lei Liu, Hui Shen, Tingting Liu, Jing Jin, Nanxi Yu, Zhijie Wan, Hang Wang, Xuguang Hu, Yuanyuan Chen, Jianming Cai
Summary: This study reveals that the lncRNA ANRIL targets the miR-7-5p/PARP1 axis to regulate DNA damage repair, suggesting that modulating ANRIL expression could be a promising approach to overcome radiation resistance.
Article
Microbiology
Jillian Romsdahl, Zachary Schultzhaus, Amy Chen, Jing Liu, Alexander Ewing, Judson Hervey, Zheng Wang
Summary: Fungi exhibit resistance to high levels of ionizing radiation, which can be increased through adaptive laboratory evolution. By using black yeast Exophiala dermatitidis, researchers demonstrated that gamma-radiation resistance can be greatly enhanced through repeated rounds of irradiation and outgrowth, leading to the identification of genetic mutations associated with ionizing radiation resistance. Disruption of the non-homologous end-joining pathway was found to greatly increase resistance to gamma-radiation in E. dermatitidis, suggesting the importance of homologous and non-homologous repair pathways in fungal radiation resistance.
ENVIRONMENTAL MICROBIOLOGY
(2021)
Article
Environmental Sciences
Masahiro Hosoda, Eka Djatnika Nugraha, Naofumi Akata, Ryohei Yamada, Yuki Tamakuma, Michiya Sasaki, Kevin Kelleher, Shinji Yoshinaga, Takahito Suzuki, Chanis Pornnumpa Rattanapongs, Masahide Furukawa, Masaru Yamaguchi, Kazuki Iwaoka, Tetsuya Sanada, Tomisato Miura, Kusdiana, Dadong Iskandar, Eko Pudjadi, Ikuo Kashiwakura, Shinji Tokonami
Summary: The study found a unique high natural radiation area in Indonesia where residents are exposed to chronic low dose-rate radiation. Indoor radon concentrations exceeded the reference levels recommended by the World Health Organization, and outdoor radon concentrations were comparable to high indoor levels. The annual effective dose due to external and internal exposures in the study area exceeded the dose limit for radiation workers, suggesting the need for further epidemiological studies on health effects.
SCIENCE OF THE TOTAL ENVIRONMENT
(2021)
Article
Biotechnology & Applied Microbiology
Vinay Jain, P. R. Vivek Kumar, P. K. M. Koya, G. Jaikrishan, Birajalaxmi Das
MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS
(2016)
Article
Multidisciplinary Sciences
Vinay Jain, Birajalaxmi Das
Article
Biology
Vinay Jain, P. A. Hassan, Birajalaxmi Das
INTERNATIONAL JOURNAL OF RADIATION BIOLOGY
(2014)
Article
Cell Biology
Divyalakshmi Saini, Shridevi Shelke, A. Mani Vannan, Sneh Toprani, Vinay Jain, Birajalaxmi Das, M. Seshadri
MOLECULAR AND CELLULAR BIOCHEMISTRY
(2012)
Article
Biology
Divyalakshmi Saini, K. R. Sudheer, P. R. Vivek Kumar, D. C. Soren, Vinay Jain, P. K. M. Koya, G. Jaikrishan, Birajalaxmi Das
INTERNATIONAL JOURNAL OF RADIATION BIOLOGY
(2020)
Article
Immunology
Divyashri Baraniya, Vinay Jain, Ronald Lucarelli, Vincent Tam, Lisa Vanderveer, Sumant Puri, Maobin Yang, Nezar Noor Al-hebshi
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2020)
Article
Oncology
Vinay Jain, Divyashri Baraniya, Doaa E. El-Hadedy, Tsute Chen, Michael Slifker, Fadhl Alakwaa, Kathy Q. Cai, Kumaraswamy N. Chitrala, Christopher Fundakowski, Nezar N. Al-Hebshi
Summary: This study used laser microdissection and deep metatranscriptome sequencing to simultaneously characterize the microbiome and host transcriptomes in oral squamous cell carcinoma (OSCC). The results showed the presence of a low abundance yet transcriptionally active, unique multi-kingdom microbiome in OSCC tissues, mainly composed of bacteria and bacteriophages. The enriched taxa in OSCC were associated with upregulation of proliferation-related pathways. These findings provide new insights into the potential mechanisms by which the microbiome contributes to oral carcinogenesis.
CANCER RESEARCH COMMUNICATIONS
(2023)
Article
Biotechnology & Applied Microbiology
Divyalakshmi Saini, Vinay Jain, Birajalaxmi Das
Summary: The study on the biological effects of chronic low dose ionizing radiation exposure in Kerala coast revealed that natural radiation exposure did not have any adverse effect on telomere length, but showed differences in transcriptional levels of telomere and DNA repair genes, indicating their role in radio-adaptive response.
MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS
(2022)
Article
Biotechnology & Applied Microbiology
C. F. M. Menck, R. S. Galhardo, A. Quinet
Summary: Studies have shown that xeroderma pigmentosum variant (XP-V) patients have mutations in the POLH gene, resulting in a high frequency of skin tumors. However, it is paradoxical that the translesion synthesis DNA polymerase eta (Pol η) in these patients can actually suppress mutations, and the mechanism behind this is still unclear. Recent evidence suggests that cyclobutane pyrimidine dimers (CPDs) play an instructional role for Pol η, enabling accurate replication of these lesions, and the mutagenic effects induced by UV radiation are caused by the deamination of C-containing CPDs. This process leads to C>T transitions, which are the most common mutations in skin cancers. The delayed replication in XP-V cells amplifies the deamination of C in CPDs and increases the burden of C>T mutations through the activity of backup TLS polymerases.
MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS
(2024)
