Article
Biochemistry & Molecular Biology
Nicole Kaminski, Anne R. Wondisford, Youngho Kwon, Michelle Lee Lynskey, Ragini Bhargava, Jonathan Barroso-Gonzalez, Laura Garcia-Exposito, Boxue He, Meng Xu, Dattatreya Mellacheruvu, Simon C. Watkins, Mauro Modesti, Kyle M. Miller, Alexey Nesvizhskii, Huaiying Zhang, Patrick Sung, Roderick J. O'Sullivan
Summary: In this study, the researchers found that RAD51AP1 interacts with TERRA and utilizes it to generate D and R-loop HR intermediates. RAD51AP1 binds to and stabilizes TERRA-containing R-loops, playing a role in the suppression of TERRA and prevention of TRCs during ALT-HDR. These findings provide insights into the important role of RAD51AP1 in the ALT mechanism and regulation of TERRA.
Review
Oncology
Michal Kroupa, Kristyna Tomasova, Miriam Kavec, Pavel Skrobanek, Tomas Buchler, Rajiv Kumar, Ludmila Vodickova, Pavel Vodicka
Summary: Telomeres are complex protective structures at the ends of linear eukaryotic chromosomes. Telomeric transcripts, especially TERRA, play crucial roles in maintaining genomic stability and gene expression. Understanding the telomere transcriptome is essential for telomere function and human pathology, and may have clinical opportunities in cancer precision medicine.
FRONTIERS IN ONCOLOGY
(2022)
Review
Oncology
Folake Orafidiya, Lin Deng, Charlotte Lynne Bevan, Claire Emily Fletcher
Summary: Non-coding RNAs play important roles in tumor, especially in response to DNA damage. Studying these non-coding RNAs can help design better treatments and tests for prostate cancer.
Article
Oncology
Francesca Scionti, Giada Juli, Roberta Rocca, Nicoletta Polera, Matteo Nadai, Katia Grillone, Daniele Caracciolo, Caterina Riillo, Emanuela Altomare, Serena Ascrizzi, Basilio Caparello, Maria Cerra, Mariamena Arbitrio, Sara N. N. Richter, Anna Artese, Stefano Alcaro, Pierosandro Tagliaferri, Pierfrancesco Tassone, Maria Teresa Di Martino
Summary: In this study, the researchers found that a small molecule called hit 17 could stabilize the structure of TERRA, causing the dissociation of TRF2 from telomeres in multiple myeloma (MM) cell lines. This led to activation of the DNA damage response, cell cycle arrest, proliferation block, and apoptotic death. Furthermore, hit 17 demonstrated anti-tumor activity in MM xenograft models.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2023)
Review
Biochemistry & Molecular Biology
Siti A. M. Imran, Muhammad Dain Yazid, Wei Cui, Yogeswaran Lokanathan
Summary: TRF2 plays a crucial role in protecting telomeres and preventing DNA instability and diseases like cancer. Despite its ability to inhibit DNA damage response factors, more research is needed to understand its interactions outside of telomeres.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cell Biology
Audrey Chansard, Enrico Pobega, Pierre Caron, Sophie E. Polo
Summary: The organization of chromatin has a significant impact on DNA damage repair. Heterochromatin, through transcriptional silencing, plays a vital role in maintaining genome integrity and cellular homeostasis. Understanding the effect of heterochromatin on the DNA damage response is critical, and this study presents two laser micro-irradiation-based methods for imaging the DDR in heterochromatin domains in mammalian cells.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
C. E. Fletcher, L. Deng, F. Orafidiya, W. Yuan, M. P. G. S. Lorentzen, O. W. Cyran, A. Varela-Carver, T. A. Constantin, D. A. Leach, F. M. Dobbs, I Figueiredo, B. Gurel, E. Parkes, D. Bogdan, R. R. Pereira, S. G. Zhao, A. Neeb, F. Issa, J. Hester, H. Kudo, Y. Liu, Y. Philippou, R. Bristow, K. Knudsen, R. J. Bryant, F. Y. Feng, S. H. Reed, I. G. Mills, J. de Bono, C. L. Bevan
Summary: miR-346 induces rapid and extensive DNA damage in prostate cancer cells through transcriptional hyperactivation, R-loop formation, and replication stress. It disrupts the interaction between NORAD and PUM2, leading to PUM2 stabilization and increased turnover of DNA damage response transcripts. miR-346 downregulates target transcripts preferentially at binding sites of highly transcriptionally active transcription factors. Targeting miR-346 may enhance the sensitivity of prostate cancer cells to DNA-damaging drugs and induce tumor regression as a monotherapy.
Article
Medicine, Research & Experimental
Songzhu Zou, Xiaomei Gou, Kunming Wen
Summary: DNA damage and repair are critical in cancer development, progression, and treatment. Various types of DNA damage elicit DNA damage responses and subsequent repair processes. Long non-coding RNAs (lncRNAs) can regulate DNA damage repair by interacting with RNA binding proteins (RBPs), particularly in the repair of DNA double-strand breaks (DSBs). This review focuses on discussing the regulatory effects of lncRNAs and RBPs on DNA damage repair, specifically DSB repair, and its implications in cancer.
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Arpita Saha, Amit Kumar Gaurav, Unnati M. Pandya, Marjia Afrin, Ranjodh Sandhu, Vishal Nanavaty, Brittny Schnur, Bibo Li
Summary: In this study, several unique features of TERRA and telomere biology in Trypanosoma brucei were identified. It was found that TERRA foci number is cell cycle-regulated and influenced by TbTRF. TbTRF binds TERRA through its C-terminal Myb domain in a sequence-specific manner, suppressing TERRA levels without affecting its half-life, and depletion of TbTRF leads to increased telomeric R-loop and telomere DNA damage.
NUCLEIC ACIDS RESEARCH
(2021)
Review
Biochemistry & Molecular Biology
Natalia Slawinska, Renata Krupa
Summary: Cells can become senescent in response to stress, which can be beneficial in some cases like suppressing tumour development or promoting tissue repair, but may also contribute to the ageing process.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Caterina Manzato, Luca Larini, Claudio Oss Pegorar, Maria Rosaria Dello Stritto, Katarina Jurikova, Verena Jantsch, Emilio Cusanelli
Summary: This study reports the expression of TERRA in Caenorhabditis elegans. TERRA is regulated by the telomere-binding proteins POT-1 and POT-2, and its transcripts are heterogeneous in length and form discrete nuclear foci. In germ cells, TERRA is expressed in all stages of meiotic prophase I, and it is upregulated prior to activation of the alternative lengthening mechanism (ALT).
NUCLEIC ACIDS RESEARCH
(2023)
Article
Cell Biology
Tan Phat Pham, Diewertje I. Bink, Laura Stanicek, Anke van Bergen, Esmee van Leeuwen, Yvonne Tran, Ljubica Matic, Ulf Hedin, Ilka Wittig, Stefanie Dimmeler, Reinier A. Boon
Summary: Aging is accompanied by various physiological changes, leading to cardiovascular diseases due to impaired vascular homeostasis. Increased DNA damage is a hallmark of aging, which can be repaired by the DNA signaling and repair system. In this study, it was found that long non-coding RNA Aerrie plays a role in DNA repair mechanism, affecting endothelial cell function and genomic stability.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Biology
Serge Bauwens, Liudmyla Lototska, Stephane Koundrioukoff, Michelle Debatisse, Jing Ye, Eric Gilson, Aaron Mendez-Bermudez
Summary: The study revealed that TRF2 plays a crucial role in pericentromeric heterochromatin replication by regulating both replication initiation and elongation, impacting the replication activity of pericentromeric DNA.
Review
Biochemistry & Molecular Biology
Jitendra Thakur, Jenika Packiaraj, Steven Henikoff
Summary: Satellite DNA is composed of tandem repeats that are involved in cellular processes such as chromosome segregation. Most satellite DNA sequences are found at chromosome ends and exhibit high repetitiveness. While satellite DNA is often absent in genome assemblies, some sequences can be transcribed into non-coding RNAs, influencing their function.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Joshua Victor, Jamie Deutsch, Annalis Whitaker, Erica N. Lamkin, Anthony March, Pei Zhou, Jason W. Botten, Nimrat Chatterjee
Summary: SARS-CoV-2 infection may trigger a DNA damage response in host cells, leading to telomere shortening and reduced expression of the TRF2 shelterin-protein complex.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Vadirn Shchepachev, Harry Wischnewski, Charlotte Soneson, Andreas W. Arnold, Claus M. Azzalin
Article
Biochemistry & Molecular Biology
Martin Moravec, Harry Wischnewski, Amadou Bah, Yan Hu, Na Liu, Lorenzo Lafranchi, Megan C. King, Claus M. Azzalin
Article
Biochemistry & Molecular Biology
Stephanie Heinrich, Corinne L. Sidler, Claus M. Azzalin, Karsten Weis
Article
Cell Biology
Isabella M. Y. Zanini, Charlotte Soneson, Luca E. Lorenzi, Claus M. Azzalin
JOURNAL OF CELL SCIENCE
(2017)
Article
Endocrinology & Metabolism
Florian Buettner, Kyle Jay, Harry Wischnewski, Thomas Stadelmann, Shady Saad, Konstantins Jefimovs, Madina Mansurova, Juan Gerez, Claus M. Azzalin, Reinhard Dechant, Alfredo J. Ibanez
Article
Biochemistry & Molecular Biology
Yong Woo Lee, Rajika Arora, Harry Wischnewski, Claus M. Azzalin
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2018)
Article
Biochemistry & Molecular Biology
Yong Woo Lee, Rajika Arora, Harry Wischnewski, Claus M. Azzalin
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2018)
Article
Multidisciplinary Sciences
Bruno Silva, Richard Pentz, Ana Margarida Figueira, Rajika Arora, Yong Woo Lee, Charlotte Hodson, Harry Wischnewski, Andrew J. Deans, Claus M. Azzalin
NATURE COMMUNICATIONS
(2019)
Article
Genetics & Heredity
Yan Hu, Henrietta W. Bennett, Na Liu, Martin Moravec, Jessica F. Williams, Claus M. Azzalin, Megan C. King
Article
Biochemistry & Molecular Biology
Edna Gicela Ortiz Morea, Elton Jose Rosas Vasconcelos, Cristiane de Santis Alves, Selma Giorgio, Peter J. Myler, Helio Langoni, Claus Maria Azzalin, Maria Isabel Nogueira Cano
Summary: TERRA, a noncoding RNA crucial for telomere regulation, is transcribed from the subtelomeric region in various life stages of parasites and shares conserved features with other eukaryotes. Additionally, TERRA may control telomere length changes through regulating telomeric base J levels, while also playing a role in telomere protection, especially in infective forms of parasites.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2021)
Article
Multidisciplinary Sciences
Bruno Silva, Rajika Arora, Silvia Bione, Claus M. Azzalin
Summary: TERRA transcription actively destabilizes telomere integrity in ALT cells, thereby triggering BIR and promoting telomere elongation.
NATURE COMMUNICATIONS
(2021)
Article
Biology
Joao C. Sabino, Madalena R. de Almeida, Patricia L. Abreu, Ana M. Ferreira, Paulo Caldas, Marco M. Domingues, Nuno C. Santos, Claus M. Azzalin, Ana Rita Grosso, Sergio Fernandes de Almeida
Summary: The activity of TET enzymes promotes the formation of R-loops, revealing new mechanisms of gene expression regulation.
Article
Biochemistry & Molecular Biology
Patricia L. Abreu, Yong Woo Lee, Claus M. Azzalin
Summary: RNA-protein interactions play crucial roles in cellular pathways such as protein translation, nuclear organization, and genome stability maintenance. The binding of TRF1 and TRF2 to TERRA depends on the latter's ability to form G-quadruplex structures. The inhibitory activity of TRF1 on TERRA-B domain complex formation is mainly mediated by a patch of glutamates within its N-terminal A domain.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Bruno Silva, Rajika Arora, Claus M. Azzalin
Summary: This study demonstrates that telomere transcription is a major trigger of alternative lengthening of telomeres (ALT) activity. Inhibiting the transcription of telomeric long noncoding RNA TERRA can suppress ALT features. Additionally, experimentally increasing TERRA transcription leads to rapid loss of telomeric DNA.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biochemistry & Molecular Biology
Nikenza Viceconte, Axelle Loriot, Patricia Lona Abreu, Marion Scheibe, Albert Fradera Sola, Falk Butter, Charles De Smet, Claus M. Azzalin, Nausica Arnoult, Anabelle Decottignies
Summary: TERRA molecules play important roles in telomeres, with mouse and human TERRA likely to have similar functions in cells.
Article
Biochemistry & Molecular Biology
Kun He, Mengyi Xie, Weifeng Hong, Yonghe Li, Yaolin Yin, Xiaojin Gao, Yi He, Yu Chen, Chuan You, Jingdong Li
Summary: Centromere protein L (CENPL) is overexpressed in hepatocellular carcinoma (HCC) and is associated with poor patient prognosis. Upregulation of CENPL promotes tumor proliferation and glycolysis in HCC cells by activating the MEK1/2-ERK1/2 signaling pathway.
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY
(2024)
Article
Biochemistry & Molecular Biology
Yingzi Wang, Haozhong Huang, Huimin Weng, Chunsen Jia, Bin Liao, Yang Long, Fengxu Yu, Yongmei Nie
Summary: Talin protein plays a crucial role in transmitting mechanical forces by connecting the extracellular matrix to the cytoskeleton. It converts mechanical signals into biochemical signals and serves as diagnostic, therapeutic, and prognostic indicators in diseases.
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY
(2024)
Review
Biochemistry & Molecular Biology
Hema Saranya Ilamathi, Marc Germain
Summary: Mitochondria are the central metabolic hubs in cells, relying on proteins encoded by nuclear DNA and mitochondrial DNA (mtDNA) for their function. The maintenance and distribution of mtDNA are crucial for proper mitochondrial function and are associated with mitochondrial diseases. mtDNA is organized into nucleoids that dynamically move and interact with each other. The replication and distribution of mtDNA nucleoids are regulated by the complex interplay of mitochondrial dynamics, ER-mitochondria contact sites, and cytoskeletal networks.
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY
(2024)
Article
Biochemistry & Molecular Biology
K. K. Sruthi, Sirisha Natani, Ramesh Ummanni
Summary: The overexpression of TPD52 is associated with the emergence of neuroendocrine prostate cancer (NEPC). TPD52 activates the NF-kappa B - STAT3 axis to induce neuroendocrine differentiation (NED) of prostate cancer cells. Therapeutic targeting of TPD52 is important for the treatment of prostate cancer.
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY
(2024)
Article
Biochemistry & Molecular Biology
Cui Li, Feifan Xiang, Yuqi Gong, Yi Fu, Ge Chen, Zhi Wang, Zhong Li, Daiqing Wei
Summary: Our study demonstrates the significant role of tumor-derived microparticles (T-MPs) in osteosarcoma metastasis and immune response. T-MPs promote macrophage polarization and stimulate migration and chemoresistance of osteosarcoma cells, thereby affecting the progression of osteosarcoma.
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY
(2024)