Article
Multidisciplinary Sciences
Ilaria Rosso, Corey Jones-Weinert, Francesca Rossiello, Matteo Cabrini, Silvia Brambillasca, Leonel Munoz-Sagredo, Zeno Lavagnino, Emanuele Martini, Enzo Tedone, Massimiliano Garre, Julio Aguado, Dario Parazzoli, Marina Mione, Jerry W. Shay, Ciro Mercurio, Fabrizio d'Adda di Fagagna
Summary: This study found that telomeric dilncRNAs are significantly elevated in ALT cells, and inhibition of teloC dilncRNAs leads to DNA replication stress responses, increased genomic instability, and selective induction of apoptosis in ALT cells. These results reveal the essential role of teloC dilncRNA in coordinating the recruitment of DDR factors to ALT telomeres and the survival of ALT cancer cells.
NATURE COMMUNICATIONS
(2023)
Article
Genetics & Heredity
Christopher B. Nelson, Taghreed M. Alturki, Jared J. Luxton, Lynn E. Taylor, David G. Maranon, Keiko Muraki, John P. Murnane, Susan M. Bailey
Summary: The study reveals that telomeric double-strand breaks in human G1 cells activate early DNA damage responses, but do not show localization of important recombination regulator 53BP1 and lack evidence of classical non-homologous end-joining and homologous recombination. Instead, telomeric DSBs in G1 cells lead to extensive tracks of resected 5' C-rich telomeric single-stranded DNA, indicating potential involvement of alternative lengthening of telomere pathway.
FRONTIERS IN GENETICS
(2021)
Editorial Material
Genetics & Heredity
Katarina Jurikova, Peter De Wulf, Emilio Cusanelli
Summary: Long noncoding RNAs derived from telomeres help to maintain telomere length and stability through various mechanisms, such as regulating telomerase activity and recombination-based telomere maintenance. New findings in yeast propose a model where telomere attachment to the nuclear envelope regulates telomere transcription and maintenance.
TRENDS IN GENETICS
(2021)
Article
Oncology
Tawna L. Mangosh, Wisam N. Awadallah, Magdalena M. Grabowska, Derek J. Taylor
Summary: In AR-independent castration-resistant prostate cancer, an atypical ALT-like phenotype and elevated SLX4IP expression are observed, while AR-dependent models lack ALT hallmarks; overexpression of SLX4IP promotes an ALT-like phenotype and telomere maintenance, whereas its deficiency accelerates telomere loss and senescence.
MOLECULAR CANCER RESEARCH
(2021)
Article
Multidisciplinary Sciences
Valentina Buemi, Odessa Schillaci, Mariangela Santorsola, Deborah Bonazza, Pamela Veneziano Broccia, Annie Zappone, Cristina Bottin, Giulia Dell'Omo, Sylvie Kengne, Stefano Cacchione, Grazia Daniela Raffa, Silvano Piazza, Fabrizio D'Adda di Fagagna, Roberta Benetti, Maurizio Cortale, Fabrizio Zanconati, Giannino Del Sal, Stefan Schoeftner
Summary: Researchers have found that the trimethylguanosine capping of the RNA component of the human telomerase complex plays an important role in directing telomere maintenance and suppressing the ALT pathway in cancer cells.
NATURE COMMUNICATIONS
(2022)
Review
Biochemistry & Molecular Biology
Bibo Li
Summary: Telomere maintenance is crucial for genome stability and regulation of antigenic variation in microbial pathogens. Trypanosomes, such as T. brucei, use a unique DNA polymerase, PolIE, to coordinate the synthesis of telomere G- and C-strands, in contrast to mammalian cells that rely on telomere proteins. Understanding these mechanisms can aid in the development of treatments for diseases caused by these pathogens.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Golam Mustafa, Sajad Shiekh, G. C. Keshav, Sanjaya Abeysirigunawardena, Hamza Balci
Summary: The accessibility of telomeric DNA is influenced by its length, with longer telomeres forming more compact structures that are less accessible to binding molecules. Intermediate regions of telomeric DNA were found to be more accessible compared to the ends, suggesting a gradient of accessibility along the telomere length. These findings highlight the importance of telomere structure in regulating accessibility to critical genomic sites.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Multidisciplinary Sciences
Fei Li, Yizhe Wang, Inah Hwang, Ja-Young Jang, Libo Xu, Zhong Deng, Eun Young Yu, Yiming Cai, Caizhi Wu, Zhenbo Han, Yu-Han Huang, Xiangao Huang, Ling Zhang, Jun Yao, Neal F. Lue, Paul M. Lieberman, Haoqiang Ying, Jihye Paik, Hongwu Zheng
Summary: Through genetic screens, researchers identify histone lysine demethylase KDM2A as a molecular vulnerability in ALT-dependent cancer cells and demonstrate its role in the resolution of ALT-specific telomere clusters via recruitment of SENP6.
NATURE COMMUNICATIONS
(2023)
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
Multidisciplinary Sciences
Adriana K. Alexander, Edward J. Rice, Jelena Lujic, Leah E. Simon, Stephanie Tanis, Gilad Barshad, Lina Zhu, Jyoti Lama, Paula E. Cohen, Charles G. Danko
Summary: During meiotic prophase I, balance between transcriptional activation and homologous recombination is crucial. We investigated the interplay between chromatin accessibility and transcription through prophase I and found that Pol II is initially in a paused state and later released in a burst mediated by transcription factors A-MYB and BRDT. This transcriptional activity is separate from meiotic recombination, which shows earlier chromatin accessibility and distinct loci from transcriptional activation. Our findings reveal mechanisms underlying chromatin specialization in transcription or recombination during meiosis.
NATURE COMMUNICATIONS
(2023)
Article
Cell Biology
Meagan Jezek, Winny Sun, Maraki Y. Negesse, Zachary M. Smith, Alexander Orosz, Erin M. Green
Summary: Set1 is an H3K4 methyltransferase involved in various genomic functions. It plays a role in subtelomeric gene repression through its catalytic activity towards H3K4 and regulates telomere length through its catalytic activity but likely independent of the H3K4 substrate. Set1 also calibrates the abundance of critical telomere maintenance proteins through transcriptional and posttranscriptional pathways. These findings provide new insights into the roles of Set1 in telomere maintenance and have implications for Set1-related methyltransferases in other systems.
MOLECULAR BIOLOGY OF THE CELL
(2023)
Article
Biochemistry & Molecular Biology
Tobias Schmidt, Adrianna Dabrowska, Joseph A. Waldron, Kelly Hodge, Grigorios Koulouras, Mads Gabrielsen, June Munro, David C. Tack, Gemma Harris, Ewan McGhee, David Scott, Leo M. Carlin, Danny Huang, John Le Quesne, Sara Zanivan, Ania Wilczynska, Martin Bushell
Summary: This study shows that single-stranded RNA sequence motifs can activate eIF4A1, leading to structural rearrangement and translation of highly structured oncogene mRNAs. These eIF4A1-dependent mRNAs contain AG-rich motifs within their 5'UTR, which specifically activate eIF4A1 unwinding and make them sensitive to eIF4A1-inhibition.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Genetics & Heredity
Syed Zahid, Sarah Aloe, Jeanette H. Sutherland, William K. Holloman, Neal F. Lue
Summary: Pot1 plays multifaceted roles in telomere maintenance and protection. It interacts with DNA repair factors, such as Rad51 and Brh2, in a context-dependent manner. Pot1 negatively regulates the recombination activities of Rad51 and Brh2 to protect telomeres when they become dysfunctional.
