Article
Cell Biology
Daniel I. Sullivan, Fiona M. Bello, Agustin Gil Silva, Kevin M. Redding, Luca Giordano, Angela M. Hinchie, Kelly E. Loughridge, Ana L. Mora, Melanie Konigshoff, Brett A. Kaufman, Michael J. Jurczak, Jonathan K. Alder
Summary: Mitochondria play important roles in cellular metabolism and signaling. Defects in mitochondria caused by genetic or acquired factors can lead to various pathologies, including premature cellular senescence. In this study, we investigated the effects of dysfunctional telomeres on mitochondrial biogenesis and function during senescence. Our results showed that senescent cells had increased mitochondrial respiratory capacity and volume. Even in vivo, hepatocytes with dysfunctional telomeres maintained their mitochondrial respiratory capacity. The upregulation of genes related to mitochondria was observed during senescence in fibroblasts and hepatocytes. These findings suggest that mitochondrial function and activity are preserved in telomere dysfunction-induced senescence.
Review
Biochemistry & Molecular Biology
Semih Can Akincilar, Claire Hian Tzer Chan, Qin Feng Ng, Kerem Fidan, Vinay Tergaonkar
Summary: Telomerase activation is a common feature in cancer, but it does not directly correlate with telomere length. Aberrant expression of shelterin proteins and their release from shortened telomeres can further promote cancer through non-canonical mechanisms.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2021)
Article
Cell Biology
M. Donatella Semeraro, Gunter Almer, Wilfried Renner, Hans-Juergen Gruber, Markus Herrmann
Summary: This study questions the utility of RTL in PBMCs as a biomarker for individual aging assessment.
Article
Cell Biology
Jue Lin, Elissa Epel
Summary: Short telomeres may increase the risk of degenerative diseases, with stress-induced telomere damage being an important pathway. The initial setting point of telomere length at birth appears to be influential, possibly affected by stress. Intergenerational stress effects on telomeres include prenatal stress and direct inheritance of short telomeres.
AGEING RESEARCH REVIEWS
(2022)
Article
Biochemistry & Molecular Biology
Robert C. Monsen, Srinivas Chakravarthy, William L. Dean, Jonathan B. Chaires, John O. Trent
Summary: The study used an integrated structural biology approach to characterize the structure of telomeric overhang, revealing that single-stranded sequences fold into multimeric structures with a maximum number of G4 units. The flexibility of these structures was investigated through molecular dynamics simulations, identifying unique sites for drug targeting.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Cell Biology
Maria Donatella Semeraro, Gunter Almer, Wilfried Renner, Hans-Juergen Gruber, Markus Herrmann
Summary: Obesity and exercise may modify age-related telomere shortening by regulating telomerase and shelterins, but existing studies are inconsistent and limited in scope.
Review
Oncology
Peter Lansdorp
Summary: The number of telomere repeats varies greatly between chromosomes, cells, and species. Loss of telomere repeats limits cell proliferation and contributes to aging, but the mechanisms behind these processes are still not fully understood. Further research is needed to investigate the role of factors such as damaged telomeric DNA, replication errors, chromatin structure, and secondary DNA structures in telomere dynamics in different cell types.
FRONTIERS IN ONCOLOGY
(2022)
Article
Biology
Shuntaro Takahashi, Sudipta Bhowmik, Shinobu Sato, Shigeori Takenaka, Naoki Sugimoto
Summary: The relationship between G4 structures and DNA replication was studied, and it was found that different ligands have different effects on the topology of G4. Some ligands can inhibit the replication of G4 with anti-parallel topology, while others selectively inhibit G4 with anti-parallel and hybrid topology. The experiments suggest that native human telomere G4 is more flexible than the modified sequence and can interact with ligands.
Article
Chemistry, Multidisciplinary
Ismail A. Elhaty
Summary: The study found that the quinazoline derivative GW2974 has a strong affinity for human telomeric G-quadruplex, and can inhibit telomerase enzyme activity by altering the stability of G-quadruplex DNA.
Article
Oncology
Anna Deregowska, Monika Pepek, Iwona Solarska, Marcin M. Machnicki, Katarzyna Pruszczyk, Marek Dudzinski, Joanna Niesiobedzka-Krezel, Ilona Seferynska, Waldemar Sawicki, Maciej Wnuk, Tomasz Stoklosa
Summary: In this study, the telomeric complex expression and function in the molecular pathogenesis of CML were analyzed. It was found that the telomere length in CD34+ CML cells shortened during the progression of the disease, which was correlated with the expression level of BCR::ABL1 transcript but not with telomerase activity. The increased expression of BCR::ABL1 was positively correlated with the expression of TRF2, RAP1, TPP1, DKC1, TNKS1, and TNKS2 genes. These findings provide insight into the mechanisms responsible for the genomic instability of leukemic cells and CML progression.
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Valeria Libera, Federico Bianchi, Barbara Rossi, Francesco D'Amico, Claudio Masciovecchio, Caterina Petrillo, Francesco Sacchetti, Alessandro Paciaroni, Lucia Comez
Summary: This study found that during the thermal melting process of G4 structure, the hydrogen-bonded network of water molecules undergoes rearrangement, which is closely related to the DNA rearrangement. Understanding the structural properties of the solvent can contribute to a better understanding of the interaction between G4s and ligands.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biology
Hueng-Chuen Fan, Fung-Wei Chang, Jeng-Dau Tsai, Kao-Min Lin, Chuan-Mu Chen, Shinn-Zong Lin, Ching-Ann Liu, Horng-Jyh Harn
Summary: Telomeres cap the ends of eukaryotic chromosomes and are essential for genome protection and replication. The maintenance of telomere length is regulated by various factors and dysfunctions in telomere maintenance and telomerase activation are associated with diseases, particularly cancer. Understanding the molecular mechanisms behind telomere length regulation and protection is crucial for future therapeutic opportunities.
Article
Cell Biology
Seongki Min, So Mee Kwon, Jiwon Hong, Young-Kyoung Lee, Tae Jun Park, Su Bin Lim, Gyesoon Yoon
Summary: This study found that the expression of mitoribosomal proteins (MRPs) decreases during the early-to-middle transition of cellular senescence, accompanied by the suppression of TPP1. These findings suggest that mitoribosomal deregulation could be an early event initiating mitochondrial dysfunction, cellular senescence, and telomere deprotection.
Article
Chemistry, Multidisciplinary
Soumi Biswas, Shubhanwita Basak, Satyabrata Samui, Sanjeev Pasadi, K. Muniyappa, Jishu Naskar
Summary: This study describes the co-assembly of a synthetic dendron-like peptide, C-delta 3-(YYEE)-E, with G4 DNA in aqueous buffer containing Na+ ions. Biophysical and molecular docking studies have confirmed the co-assembly phenomenon and the peptide's ability to enhance the thermal stability of G4 DNA. The peptide inhibits telomerase activity and down-regulates oncogenic expression, exhibiting significant cytotoxic effects on cancer cells compared to non-cancer cells.
Article
Cell Biology
Zhe Yang, Keshav Sharma, Titia de Lange
Summary: Telomeric DNA replication is dependent on TRF1, which recruits BLM helicase. However, the extensive telomere fragility and ATR signaling induced by TRF1 deletion cannot be fully explained by the loss of BLM. This study identifies TFIIH as a critical effector of TRF1 in telomere replication, and mutations in TRF1 helices cause severe replication defects independent of ATR signaling.
GENES & DEVELOPMENT
(2022)
Article
Biochemistry & Molecular Biology
Malligarjunan Rajavel, Tivadar Orban, Mengyuan Xu, Wilnelly Hernandez-Sanchez, Maria de la Fuente, Krzysztof Palczewski, Derek J. Taylor
NUCLEIC ACIDS RESEARCH
(2016)
Article
Cell Biology
Xuehuo Zeng, Wilnelly Hernandez-Sanchez, Mengyuan Xu, Tawna L. Whited, Diane Baus, Junran Zhang, Anthony J. Berdis, Derek J. Taylor
Article
Biochemistry & Molecular Biology
R. Cipriano, B. L. Bryson, K. L. S. Miskimen, C. A. Bartel, W. Hernandez-Sanchez, R. C. Bruntz, S. A. Scott, C. W. Lindsley, H. A. Brown, M. W. Jackson
Article
Biochemistry & Molecular Biology
Wilnelly Hernandez-Sanchez, Wei Huang, Brian Plucinsky, Nelson Garcia-Vazquez, Nathaniel J. Robinson, William P. Schiemann, Anthony J. Berdis, Emmanuel Skordalakes, Derek J. Taylor
Article
Multidisciplinary Sciences
Mengyuan Xu, Janna Kiselar, Tawna L. Whited, Wilnelly Hernandez-Sanchez, Derek J. Taylor
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2019)
Article
Multidisciplinary Sciences
Neetha Parameswaran, Courtney A. Bartel, Wilnelly Hernandez-Sanchez, Kristy L. Miskimen, Jacob M. Smigiel, Ahmad M. Khalil, Mark W. Jackson
SCIENTIFIC REPORTS
(2019)
Article
Biochemistry & Molecular Biology
Ankita Chadda, Alexander G. Kozlov, Binh Nguyen, Timothy M. Lohman, Eric A. Galburt
Summary: In this study, it was found that the DNA damage response in Mycobacterium tuberculosis differs from well-studied model bacteria. The DNA repair helicase UvrD1 in Mtb is activated through a redox-dependent process and is closely associated with the homo-dimeric Ku protein. Additionally, Ku protein is shown to stimulate the helicase activity of UvrD1.
JOURNAL OF MOLECULAR BIOLOGY
(2024)