Article
Cell Biology
Bohong Chen, Tianyu Ge, Meiqi Jian, Liutao Chen, Zhengwen Fang, Zibin He, Chengjing Huang, Yan An, Shanshan Yin, Yuanyuan Xiong, JingKai Zhang, Ruofei Li, Miaoman Ye, Yubing Li, Feng Liu, Wenbing Ma, Zhou Songyang
Summary: Through a genome-wide CRISPR synthetic viability screen for PARP-inhibitor resistance, Chen and Ge et al. identified a transmembrane nuclease (NUMEN) that facilitates compartmentalized and non-homologous end joining-dependent repair of double-stranded DNA breaks at the nuclear periphery. NUMEN generates short 5' overhangs through its endonuclease and 3'->5' exonuclease activities, promotes the repair of DNA lesions-including heterochromatic lamina-associated domain breaks as well as deprotected telomeres-and functions as a downstream effector of DNA-dependent protein kinase catalytic subunit. These findings highlight the role of NUMEN in DNA repair pathway choice and genome-stability maintenance, with implications for research on genome instability disorders.
NATURE CELL BIOLOGY
(2023)
Article
Biology
Elena Zaharieva, Megumi Sasatani, Ryoga Matsumoto, Kenji Kamiya
Summary: The study found that prolonged low-dose-rate radiation exposure leads to slightly increased levels of DNA repair foci, with a clear dose-response relationship. Compared to acute irradiation, low-dose-rate exposure is less efficient, and repair capacity plays an important role in the cellular response to chronic radiation.
RADIATION RESEARCH
(2021)
Article
Cell Biology
Jong-Hyuk Lee, Raghavendra A. Shamanna, Tomasz Kulikowicz, Nima Borhan Fakouri, Edward W. Kim, Louise S. Christiansen, Deborah L. Croteau, Vilhelm A. Bohr
Summary: Werner syndrome (WS) is an accelerated aging disorder characterized by genomic instability caused by WRN protein deficiency. The phosphorylation of WRN by CDK2 on serine residue 426 is critical for WRN to choose between non-homologous end joining (NHEJ) and homologous recombination (HR) pathways. The phosphorylation stabilizes WRN's affinity for RPA and enhances its role in long-range resection, a crucial step for HR.
Review
Genetics & Heredity
Bert van de Kooij, Haico van Attikum
Summary: The repair of DNA double-strand breaks plays a crucial role in maintaining genome integrity. Various pathways can repair the breaks, leading to either error-free or highly mutagenic outcomes. Genomic reporter constructs have been used extensively to study this process, allowing researchers to quantifiably assess repair by measuring the expression of fluorescent proteins. Recent advancements in genome editing technologies, such as CRISPR-Cas9, have further enhanced the utility of reporter constructs. In this review, the available DNA double-strand break repair pathway reporters will be discussed and compared, with considerations for choosing the appropriate reporter and future prospects in this field.
FRONTIERS IN GENETICS
(2022)
Article
Genetics & Heredity
Misaki Matsui, Shoki Kajita, Yuina Tsuchiya, Wakana Torii, Shiori Tamekuni, Ryotaro Nishi
Summary: Proper choice of DNA double-strand break (DSB) repair pathway is crucial for maintaining genome integrity. This study identifies USP49 as a novel enzyme that regulates ubiquitylation of DSB-induced gamma H2AX. Fine tuning of USP49 protein level and its deubiquitylation activity play important roles in cell sensitivity to DSB-inducing drug treatment.
Article
Biochemistry & Molecular Biology
Suleman S. Hussain, Rahul Majumdar, Grace M. Moore, Himanshi Narang, Erika S. Buechelmaier, Maximilian J. Bazil, Pavithran T. Ravindran, Jonathan E. Leeman, Yi Li, Manisha Jalan, Kyrie S. Anderson, Andrea Farina, Rekha Soni, Neeman Mohibullah, Edin Hamzic, Xiaoqing Rong-Mullins, Christopher Sifuentes, Rama R. Damerla, Agnes Viale, Simon N. Powell, Daniel S. Higginson
Summary: This study developed a Cas9-based repair system with simplified repair outcomes and converted it into ddPCR readouts for easier use in more laboratories. The experiment found that the key Alt-EJ factor Pol theta only accounts for 50% of total Alt-EJ, SSTR requires BRCA1 and MRE11 activity, and BRCA1 promotes Alt-EJ usage at two-ended DSBs.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Cell Biology
You-hong Wang, Zhen Guo, Liang An, Yong Zhou, Heng Xu, Jing Xiong, Zhao-qian Liu, Xiao-ping Chen, Hong-hao Zhou, Xiong Li, Tao Liu, Wei-hua Huang, Wei Zhang
Summary: This study found that LINC-PINT is significantly downregulated in nasopharyngeal cancer tissues compared to rhinitis tissues, and low LINC-PINT expressions are associated with poorer prognosis in patients receiving radiotherapy. LINC-PINT plays a functional role in inhibiting malignant phenotypes and sensitizing cancer cells to irradiation in vitro and in vivo. Mechanistically, LINC-PINT inhibits DNA damage repair through the ATM/ATR-Chk1/Chk2 signaling pathways and increases radiosensitivity by interacting with DNA-PKcs.
CELL DEATH & DISEASE
(2021)
Article
Cell Biology
Michelle L. Swift, Kate Beishline, Samuel Flashner, Jane Azizkhan-Clifford
Summary: This passage discusses the role of Sp1 in the cell cycle and its regulation of DSB repair pathway choice, favoring NHEJ repair. Sp1 is shown to recruit the NHEJ repair factor 53BP1 in G1 phase, while being evicted through phosphorylation in S phase, inhibiting HR repair.
Article
Biochemistry & Molecular Biology
Dominic Bazzano, Stephanie Lomonacol, Thomas E. Wilson
Summary: This study monitored the resection of the 5'-terminated strand at DNA double-strand breaks (DSBs) using high-throughput sequencing with molecular identifiers, revealing the roles of enzymes such as Mre11 and Exo1 in the process. Results showed a major Mre11-dependent cleavage position 60-70 bp from the DSB end and an Exo1-dependent pause point approximately 200 bp from the DSB.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Ioanna Mitrentsi, Jieqiong Lou, Adele Kerjouan, John Verigos, Bernardo Reina-San-Martin, Elizabeth Hinde, Evi Soutoglou
Summary: In this study, the spatial recruitment of HR factors upon DNA breaks was compared between human and mouse pericentromeric heterochromatin. It was found that mouse pericentromeric heterochromatin repeat clustering creates a physical barrier that requires multiple layers of de-compaction for access to repair. These findings highlight the importance of the 3D organization of heterochromatin in the spatial activation of DNA repair pathways.
Article
Multidisciplinary Sciences
Sofie Bergstrand, Eleanor M. O'Brien, Christos Coucoravas, Dominika Hrossova, Dimitra Peirasmaki, Sandro Schmidli, Soniya Dhanjal, Chiara Pederiva, Lee Siggens, Oliver Mortusewicz, Julienne J. O'Rourke, Marianne Farnebo
Summary: The study reveals that the long non-coding RNA scaRNA2 regulates the choice between error-prone NHEJ and error-free HR DNA repair by inhibiting DNA-PK. This control of DNA repair pathway choice by RNA-dependent regulation of DNA-PK catalytic activity highlights the importance of non-coding RNAs in genomic stability.
NATURE COMMUNICATIONS
(2022)
Review
Genetics & Heredity
Alice Libri, Timea Marton, Ludovic Deriano
Summary: DNA double-strand breaks are highly toxic and can be repaired via multiple DNA repair pathways. During V(D)J recombination, certain parameters restrict the repair of DSBs to the non-homologous end-joining pathway.
FRONTIERS IN GENETICS
(2022)
Article
Cell Biology
Shuyun Ma, Zeming Rong, Chen Liu, Xiaobing Qin, Xiaoyan Zhang, Qiang Chen
Summary: DNA double-strand breaks are repaired mainly by c-NHEJ and HR pathways. A novel DSB-induced microtubule dynamics stress response (DMSR) has been uncovered, promoting DSB mobility and facilitating repair. This response occurs only in G1 or G0 cells, lasts around 6 hours, and is dependent on DNA-PK and 53BP1.
JOURNAL OF CELL BIOLOGY
(2021)
Article
Oncology
Jeffrey Patterson-Fortin, Arindam Bose, Wei-Chih Tsai, Carter Grochala, Huy Nguyen, Jia Zhou, Kalindi Parmar, Jean-Bernard Lazaro, Joyce Liu, Kelsey McQueen, Geoffrey I. Shapiro, David Kozono, Alan D. D'Andrea
Summary: Inhibitors of DNA repair pathways, such as peposertib, show promise as anticancer drugs. This study identified POLQ and genes in the MMEJ pathway as key predictors of sensitivity to DNA-PK inhibition. Combined treatment with peposertib and a POLO inhibitor resulted in synthetic lethality in TP53-deficient tumor cell lines, suggesting a potential treatment strategy for TP53-mutant solid tumors.
Article
Biochemistry & Molecular Biology
Salim Abdisalaam, Shibani Mukherjee, Souparno Bhattacharya, Sharda Kumari, Debapriya Sinha, Janice Ortega, Guo-Min Li, Hesham A. Sadek, Sunil Krishnan, Aroumougame Asaithamby
Summary: NBS1 protein, in coordination with ATM and CtIP, functions as an upstream regulator that prevents cGAS from binding micronuclear DNA. Cells lacking NBS1 recruit cGAS to micronuclear DNA and activate its function.
NUCLEIC ACIDS RESEARCH
(2022)
Review
Biochemistry & Molecular Biology
Ajaz A. Bhat, Sabah Nisar, Selma Maacha, Tatiana Correa Carneiro-Lobo, Sabah Akhtar, Kodappully Sivaraman Siveen, Nissar A. Wani, Arshi Rizwan, Puneet Bagga, Mayank Singh, Ravinder Reddy, Shahab Uddin, Jean-Charles Grivel, Gyan Chand, Michael P. Frenneaux, Mushtaq A. Siddiqi, Davide Bedognetti, Wael El-Rifai, Muzafar A. Macha, Mohammad Haris
Summary: Esophageal cancer is a disease characterized by aggressive growth and poor prognosis, with high mortality rate caused by lack of targeted therapies, resistance to chemoradiation therapy, and distant metastases. The tumor microenvironment, comprised of various cell types and molecular changes, plays a significant role in the development and treatment response of esophageal cancer.
Article
Biochemistry & Molecular Biology
Albino Bacolla, Shiladitya Sengupta, Zu Ye, Chunying Yang, Joy Mitra, Ruth B. De-Paula, Muralidhar L. Hegde, Zamal Ahmed, Matthew Mort, David N. Cooper, Sankar Mitra, John A. Tainer
Summary: The study found that acetylated NEIL1 is predominantly localized in the nucleus in association with epigenetic marks of uncondensed chromatin. Chromatin immunoprecipitation followed by high-throughput sequencing revealed that AcNEIL1 binding is related to the transcription level of genes. Bioinformatic analysis showed a significant correspondence between AcNEIL1 occupancy along the genome and mutation rates.
NUCLEIC ACIDS RESEARCH
(2021)
Review
Cell Biology
Sabah Nisar, Ajaz A. Bhat, Mayank Singh, Thasni Karedath, Arshi Rizwan, Sheema Hashem, Puneet Bagga, Ravinder Reddy, Farrukh Jamal, Shahab Uddin, Gyan Chand, Davide Bedognetti, Wael El-Rifai, Michael P. Frenneaux, Muzafar A. Macha, Ikhlak Ahmed, Mohammad Haris
Summary: circRNAs are a class of evolutionarily conserved non-coding endogenous RNAs found in the eukaryotic transcriptome, with structural stability, high expression, and tissue-specific expression. They function as sponges for miRNAs and RBPs, regulators of transcription, translation, and splicing events, and play roles in various human diseases.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Sabah Nisar, Parvaiz Yousuf, Tariq Masoodi, Nissar A. Wani, Sheema Hashem, Mayank Singh, Geetanjali Sageena, Deepika Mishra, Rakesh Kumar, Mohammad Haris, Ajaz A. Bhat, Muzafar A. Macha
Summary: HNSCC is an aggressive disease with a poor patient prognosis, necessitating a comprehensive understanding of its biology; alterations in the tumor micro-environment play a critical role in regulating cancer development.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Cell Biology
Saife N. Lone, Ajaz A. Bhat, Nissar A. Wani, Thasni Karedath, Sheema Hashem, Sabah Nisar, Mayank Singh, Puneet Bagga, Bhudev Chandra Das, Davide Bedognetti, Ravinder Reddy, Michael P. Frenneaux, Wael El-Rifai, Mushtaq A. Siddiqi, Mohammad Haris, Muzafar A. Macha
Summary: The immune system plays a crucial role in regulating tumor growth, and cancer often evades immune surveillance. Recent studies have highlighted the importance of non-coding RNAs, specifically microRNAs (miRNAs), in the mechanism of immune evasion by cancer cells. miRNAs regulate the expression of immune-modulating molecules in various immune cells, as well as in tumor cells and the tumor microenvironment. This review explores the relationship between altered expression patterns of miRNAs in tumors, immune modulation, and the functional control of a wide range of immune cells, providing detailed insights into the crosstalk between tumor immune cells and their potential as prognostic markers or therapeutic agents.
SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY
(2022)
Article
Oncology
Aparna Sharma, Mayank Singh, Ravi Chauhan, Prabhat Singh Malik, Sachin Khurana, Sandeep Mathur, Sunesh Kumar, Vishnubhatla Sreenivas, Lalit Kumar
Summary: This study evaluated the role of oral metronomic therapy in patients with platinum resistant/refractory epithelial ovarian cancer, and found that the addition of pazopanib can improve survival outcomes. However, there may be some side effects such as oral mucositis and fatigue.
GYNECOLOGIC ONCOLOGY
(2021)
Review
Medicine, Research & Experimental
Sheema Hashem, Tayyiba Akbar Ali, Sabah Akhtar, Sabah Nisar, Geetanjali Sageena, Shahid Ali, Sharefa Al-Mannai, Lubna Therachiyil, Rashid Mir, Imadeldin Elfaki, Mohammad Muzaffar Mir, Farrukh Jamal, Tariq Masoodi, Shahab Uddin, Mayank Singh, Mohammad Haris, Muzafar Macha, Ajaz A. Bhat
Summary: Cancer is a major cause of death and a burden to healthcare system. Natural products, with their accessibility, applicability, and reduced cytotoxicity, have been an important source of anticancer drugs. They play a major role in cancer treatment by modulating cancer microenvironment and different signaling pathways, mainly cell death pathways and embryonic developmental pathways.
BIOMEDICINE & PHARMACOTHERAPY
(2022)
Review
Oncology
Tarang Sharma, Ashna Gupta, Ravi Chauhan, Ajaz A. Bhat, Sabah Nisar, Sheema Hashem, Sabah Akhtar, Aamir Ahmad, Mohammad Haris, Mayank Singh, Shahab Uddin
Summary: Esophageal cancer is a lethal malignancy and a major cause of cancer-related deaths worldwide. Traditional treatments have limited efficacy and poor prognosis. In addition to the tumor microenvironment, the esophageal microbiome and inflammation also play a significant role in promoting esophageal cancer.
CANCER AND METASTASIS REVIEWS
(2022)
Review
Biochemistry & Molecular Biology
Vincent E. Provasek, Joy Mitra, Vikas H. Malojirao, Muralidhar L. Hegde
Summary: The continuous process of DNA damage and repair is crucial for maintaining genomic integrity. Among different types of DNA damage, double-strand breaks (DSBs) are the most dangerous and require timely repair. DSB repair is particularly important for nondividing, post-mitotic cells in the central nervous system (CNS), as failure in these mechanisms can lead to disruptions in neural networks and motor functions. In addition to repair pathways, DNA damage response (DDR) signaling and hnRNP proteins have been found to play important roles in neuronal DSB repair and are linked to age-associated neurological disorders.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Saife N. Lone, Sabah Nisar, Tariq Masoodi, Mayank Singh, Arshi Rizwan, Sheema Hashem, Wael El-Rifai, Davide Bedognetti, Surinder K. Batra, Mohammad Haris, Ajaz A. Bhat, Muzafar A. Macha
Summary: Liquid biopsies are non-invasive methods that have revolutionized cancer diagnosis and monitoring. By analyzing tumor-derived entities in body fluids, liquid biopsies provide detailed information about tumor characteristics and can be used for detection, prognosis, and treatment monitoring.
Article
Multidisciplinary Sciences
Sharmistha Chakraborty, Mayank Singh, Raj K. Pandita, Vipin Singh, Calvin S. C. Lo, Fransisca Leonard, Nobuo Horikoshi, Eduardo G. Moros, Deblina Guha, Clayton R. Hunt, Eric Chau, Kazi M. Ahmed, Prayas Sethi, Vijaya Charaka, Biana Godin, Kalpana Makhijani, Harry Scherthan, Jeanette Deck, Michael Hausmann, Arjamand Mushtaq, Mohammad Altaf, Kenneth S. Ramos, Krishna M. Bhat, Nitika Taneja, Chandrima Das, Tej K. Pandita
Summary: This study finds that hyperthermia can inhibit DNA double-strand break repair that utilizes homologous recombination by reducing H4K16 acetylation and impacting chromatin organization. This discovery is important for understanding the effects of hyperthermia on genome stability.
Review
Oncology
Ajaz A. Bhat, Sabah Nisar, Mayank Singh, Bazella Ashraf, Tariq Masoodi, Chandra P. Prasad, Atul Sharma, Selma Maacha, Thasni Karedath, Sheema Hashem, Syed Besina Yasin, Puneet Bagga, Ravinder Reddy, Michael P. Frennaux, Shahab Uddin, Punita Dhawan, Mohammad Haris, Muzafar A. Macha
Summary: Colorectal cancer is a life-threatening cancer primarily caused by liver and peritoneal metastases. Intestinal inflammation, a known risk factor, creates an inflammatory environment enriched with various cells and factors. Aberrantly expressed cytokines and chemokines play a role in promoting CRC pathogenesis and influencing disease outcomes.
CANCER COMMUNICATIONS
(2022)
Review
Medicine, Research & Experimental
Sabah Nisar, Tariq Masoodi, Kirti S. Prabhu, Shilpa Kuttikrishnan, Lubna Zarif, Summaiya Khatoon, Shahid Ali, Shahab Uddin, Ammira Al-Shabeeb Akil, Mayank Singh, Muzafar A. Macha, Ajaz A. Bhat
Summary: This review article presents updated literature on different natural products used as chemotherapy or radiation therapy sensitizers in various solid tumors, highlighting the potential and importance of natural products in cancer treatment.
BIOMEDICINE & PHARMACOTHERAPY
(2022)
Review
Medicine, Research & Experimental
Ajaz A. Bhat, Sabah Nisar, Soumi Mukherjee, Nirmalya Saha, Nageswari Yarravarapu, Saife N. Lone, Tariq Masoodi, Ravi Chauhan, Selma Maacha, Puneet Bagga, Punita Dhawan, Ammira Al-Shabeeb Akil, Wael El-Rifai, Shahab Uddin, Ravinder Reddy, Mayank Singh, Muzafar A. Macha, Mohammad Haris
Summary: Gene editing, particularly using the CRISPR/Cas9 system, shows great potential in developing cancer models, enhancing CAR-T cells, and advancing precision medicine, but further research is needed to understand its pros and cons, establish best practices, and address social and ethical implications.
JOURNAL OF TRANSLATIONAL MEDICINE
(2022)
Review
Biochemistry & Molecular Biology
Gunjan Dagar, Rakesh Kumar, Kamlesh K. Yadav, Mayank Singh, Tej K. Pandita
Summary: The ubiquitin proteasomal system (UPS) is an essential protein degradation pathway in maintaining cellular homeostasis. It plays a critical role in various cellular processes and has become a promising target in cancer therapeutics. Dysregulation of the UPS is implicated in cancer development and progression. Current therapeutic strategies targeting UPS have shown promise, and new emerging strategies are being explored for next-generation drug development.
BIOCHIMICA ET BIOPHYSICA ACTA-GENE REGULATORY MECHANISMS
(2023)
