Review
Cell Biology
Claire Ghilain, Eric Gilson, Marie-Josephe Giraud-Panis
Summary: Protecting telomeres from the DNA damage response is crucial to prevent cellular senescence and aging; telomere DNA shortening in dividing somatic cells leads to replicative senescence, contributing to aging; the Shelterin protein complex plays a key role in protecting telomeres and its changes in structure and function during development and aging are a subject of intense research.
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
Zong Huan-Huan, Hou Kai-Long, Guo Xin, Luo Ying, Jia Shu-Ting
Summary: Telomeres are located at the ends of linear chromosomes in eukaryotic cells to maintain genome integrity and cell survival. The Shelterin complex, consisting of six telomere-specific proteins, binds to telomeric repeats to protect them from aberrant DNA damage response activation. Shelterin components not only regulate DNA repair pathways and telomere replication, but also influence the choice of repair pathways in dysfunctional telomeres.
PROGRESS IN BIOCHEMISTRY AND BIOPHYSICS
(2021)
Article
Biochemistry & Molecular Biology
Xu Li, Meijie Wang, Wei Zheng, Wei Huang, Zeyu Wang, Kairang Jin, Lin Liu, Zhongbo Yu
Summary: Chromosome stability is primarily determined by telomere length, which is regulated by the core subunit TRF1 of shelterin. Research on the dynamics of TRF1 has shown its role in telomere organization, compaction, and interaction at telomeric DNA forks. Understanding these mechanisms can facilitate future studies on telomeres and the development of shelterin-targeted drugs.
NUCLEIC ACIDS RESEARCH
(2021)
Review
Pharmacology & Pharmacy
Mohammad Shoeb, Helen C. S. Meier, James M. Antonini
Summary: Telomeres play a crucial role in protecting genetic material, preventing DNA damage and cell senescence, and influencing cell division. Inappropriate DNA repair may lead to tumorigenesis and other pathologies. Therefore, telomere length and interacting proteins have the potential to serve as biomarkers for occupational exposures and health responses.
PHARMACOLOGY & THERAPEUTICS
(2021)
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
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
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
Biochemistry & Molecular Biology
Xin Nie, Danqing Xiao, Yuanlong Ge, Yujie Xie, Haoxian Zhou, Tian Zheng, Xiaocui Li, Haiying Liu, Hui Huang, Yong Zhao
Summary: In this study, it was found that TCOF1 is recruited to telomeres during S phase by interacting with TRF2, where it suppresses telomere transcription, ensuring telomere stability.
CELL DEATH AND DIFFERENTIATION
(2021)
Article
Biology
Evan H. Lister-Shimauchi, Michael Dinh, Paul Maddox, Shawn Ahmed
Summary: Telomerase deficiency leads to transgenerational shortening of telomeres, while telomeres do not play a role in transgenerational epigenetic inheritance. Mutants lacking Pot1 or Pot2 proteins in C. elegans affect the levels of Pot1 telomere foci in offspring for multiple generations, with deficiencies in heterochromatin formation reducing Pot1 foci. These findings offer new insights into the interaction between telomere biology and transgenerational epigenetic inheritance.
COMMUNICATIONS BIOLOGY
(2021)
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
Medicine, Research & Experimental
Emmanouil Stylianakis, Jackson Ping Kei Chan, Pui Pik Law, Yi Jiang, Sanjay Khadayate, Mohammad Mahdi Karimi, Richard Festenstein, Jean-Baptiste Vannier
Summary: We found that mouse HP1 & gamme; plays a crucial role in telomere function by regulating the transcription of telomere factors and TERRAs, which has profound effects on telomere stability.
Article
Genetics & Heredity
Heloise Coutelier, Oana Ilioaia, Jeanne Le Peillet, Marion Hamon, Damien D'Amours, Maria Teresa Teixeira, Zhou Xu
Summary: Telomere dysfunction can cause cell cycle arrest, but cells can adapt and bypass the arrest after a period of time. This study shows that the protein level of Cdc5 decreases after telomere dysfunction, and this decrease is important for maintaining long-term arrest. The phosphorylation status of Cdc5 and its mutant form Cdc5-ad also play a role in adaptation efficiency.
Article
Multidisciplinary Sciences
Mandy L. Ballinger, Swetansu Pattnaik, Piyushkumar A. Mundra, Milita Zaheed, Emma Rath, Peter Priestley, Jonathan Baber, Isabelle Ray-Coquard, Nicholas Isambert, Sylvain Causeret, Winette T. A. van der Graaf, Ajay Puri, Florence Duffaud, Axel Le Cesne, Beatrice Seddon, Coonoor Chandrasekar, Joshua D. Schiffman, Andrew S. Brohl, Paul A. James, Jean-Emmanuel Kurtz, Nicolas Penel, Ola Myklebost, Leonardo A. Meza-Zepeda, Hilda Pickett, Maya Kansara, Nicola Waddell, Olga Kondrashova, John Pearson, Andrew P. Barbour, Shuai Li, Tuong L. Nguyen, Diane Fatkin, Robert M. Graham, Eleni Giannoulatou, Melissa J. Green, Warren Kaplan, Shyamsundar Ravishankar, Joseph Copty, Joseph E. Powell, Edwin Cuppen, Kristel van Eijk, Jan Veldink, Jin-Hee Ahn, Jeong Eun Kim, R. Lor Randall, Kathy Tucker, Ian Judson, Rajiv Sarin, Thomas Ludwig, Emmanuelle Genin, Jean-Francois Deleuze, Michelle Haber, Glenn Marshall, Murray J. Cairns, Jean-Yves Blay, David M. Thomas
Summary: Cancer genetics has focused on epithelial malignancies, but this study explores specific pathways related to sarcomas, rare malignancies derived from embryonic mesoderm. Germline sequencing of sporadic cases and healthy controls reveals two sarcoma-specific pathways involved in mitotic and telomere functions. Centrosome gene variants are linked to specific tumors, while heritable defects in the shelterin complex increase susceptibility to sarcomas, melanomas, and thyroid cancers. These findings highlight the role of heritable defects in mitotic and telomere biology in sarcoma risk.
Article
Medicine, Research & Experimental
Manal Mehibel, Yu Xu, Caiyun G. Li, Eui Jung Moon, Kaushik N. Thakkar, Anh N. Diep, Ryan K. Kim, Joshua D. Bloomstein, Yiren Xiao, Julien Bacal, Joshua C. Saldivar, Quynh-Thu Le, Karlene A. Cimprich, Erinn B. Rankin, Amato J. Giaccia
Summary: Hypoxia, a characteristic of the tumor microenvironment, has been shown to confer resistance to traditional chemotherapy but can synergize with PARP inhibitors under severe hypoxia. Moderate hypoxia, however, promotes resistance to PARP inhibitors. Selective elimination of hypoxic tumor cells enhances the efficacy of PARP inhibitor therapy without increasing normal tissue toxicity.
JOURNAL OF CLINICAL INVESTIGATION
(2021)
