Review
Cell Biology
Erin Bonnell, Emeline Pasquier, Raymund J. Wellinger
Summary: Telomeres, crucial for maintaining genomic stability, pose challenges for replication due to their repetitive nature and the formation of secondary structures, leading to replication fork stalling. Multiple mechanisms are involved in overcoming these obstacles to ensure efficient telomeric DNA duplication and preserve genome integrity.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Genetics & Heredity
Ryan P. Barnes, Sanjana A. Thosar, Patricia L. Opresko
Summary: Telomeres present challenges for DNA replication due to their repetitive sequences, non-B DNA structures, and the presence of nucleo-protein t-loops. Telomeres are particularly susceptible to replication stress in cancer cells, resulting in telomere fragility in metaphase cells. One mechanism cells use to cope with replication stress, including at telomeres, is DNA synthesis in mitosis (MiDAS). Although both phenomena are observed in mitotic cells, the relationship between them is poorly understood, but they are both linked by DNA replication stress. In this review, we summarize the regulation of telomere fragility and telomere MiDAS, focusing on the proteins involved in these telomere phenotypes.
Article
Biochemistry & Molecular Biology
Yajun Wang, Wei Zhu, Yumi Jang, Joshua A. Sommers, Gong Yi, Chandrakala Puligilla, Deborah L. Croteau, Yibin Yang, Mihoko Kai, Yie Liu
Summary: RBM14 is associated with telomeres and negatively regulates TERRA expression, inhibiting the formation of RNA:DNA hybrids at telomeres. It plays a role in protecting telomere integrity in human cancer cells.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Multidisciplinary Sciences
Qixiang He, Xiuhua Lin, Bianca L. Chavez, Sourav Agrawal, Benjamin L. Lusk, Ci Ji Lim
Summary: This study reveals that the CST accessory protein helps organize the Pol alpha-primase enzyme for efficient primer synthesis. Cryogenic electron microscopy structures show that CST separates the DNA and RNA catalytic centers of Pol alpha-primase into two domains and arranges them in the correct order for RNA-DNA synthesis. The study also provides insights into the template-binding specificity of CST and its role in the assembly and activation of the CST-Pol alpha-primase complex.
Article
Biochemistry & Molecular Biology
Samantha L. Sholes, Kayarash Karimian, Ariel Gershman, Thomas J. Kelly, Winston Timp, Carol W. Greider
Summary: We developed a method to tag and measure telomere length in yeast using nanopore sequencing. We observed stable chromosome-specific telomere lengths and examined the role of RIF1 and TEL1 in telomere length regulation. The study suggests the influence of Y ' elements on telomere length regulation and provides insights into possible new biological mechanisms.
Article
Biochemistry & Molecular Biology
Jielin Chen, Mingpan Cheng, Gilmar F. Salgado, Petr Stadlbauer, Xiaobo Zhang, Samir Amrane, Aurore Guedin, Fangni He, Jiri Sponer, Huangxian Ju, Jean-Louis Mergny, Jun Zhou
Summary: Research has shown that the addition of nucleotides in oligodeoxynucleotides forming intramolecular G4 structures favors the formation of a parallel fold, especially when added at the 5'end, known as the "flanking effect". This effect depends on loop arrangement and was confirmed through NMR experiments and molecular dynamics simulations.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Biology
Alexander N. Malyavko, Olga A. Petrova, Maria Zvereva, Vladimir Polshakov, Olga A. Dontsova
Summary: This study reports the functional characterization of the Rif1 homologue from the methylotrophic thermotolerant budding yeast Hansenula polymorpha DL-1. The study reveals that Rif1 in H. polymorpha suppresses telomerase-dependent telomere elongation through direct DNA binding and association with the Ku heterodimer. It is also found that Rif1 binds Stn1 and promotes its accumulation at telomeres in H. polymorpha.
Review
Biochemistry & Molecular Biology
Eugene Shakirov, Julian J-L Chen, Dorothy E. Shippen
Summary: This review summarizes the recent advances in plant telomere biology and compares it to telomere and telomerase research in other eukaryotic lineages. Despite the divergence between plants and animals over a billion years ago, the knowledge gained from plants has continued to contribute to the understanding of telomere biology and its implications for human health, aging, and stress responses. Studies of plant telomeres have revealed unexpected divergence in telomere sequence and architecture, and have provided new insights into the evolution and core components of telomerase across major eukaryotic kingdoms. Additionally, the cataloging of natural variation in plants like Arabidopsis thaliana and maize has provided valuable information on the genetic networks governing telomere length and its interactions with environmental factors and plant physiology.
Article
Biochemistry & Molecular Biology
Chih-Yi Gabriela Lin, Anna Christina Naeger, Thomas Lunardi, Aleksandra Vancevska, Gerald Lossaint, Joachim Lingner
Summary: Telomere shortening can lead to diseases and aging, often due to the lack of telomerase in cells. By developing a new isolation protocol, specific proteins associated with telomere replication can be purified, revealing their importance for maintaining telomere stability. This study provides a valuable resource for understanding the dynamic changes of the telomeric proteome during replication.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Eunkyeong Kim, Jun Kim, Chuna Kim, Junho Lee
Summary: Chromosome fusion and rearrangement triggered by telomere dysfunction can lead to genome instability. Variants generated by telomere dysfunction accumulate along all chromosomes, with diverse types of telomere damage processing observed at the nucleotide level in chromosome end structures.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Terrence Hanscom, Nicholas Woodward, Rebecca Batorsky, Alexander J. Brown, Steven A. Roberts, Mitch McVey
Summary: By computational analysis, we have identified sequence characteristics that drive successful SD-MMEJ repair and shown the necessity of DNA polymerase theta in SD-MMEJ repair at Cas9-induced breaks.
NUCLEIC ACIDS RESEARCH
(2022)
Editorial Material
Cell Biology
Fiona M. Gribble, Stephen O'Rahilly
Summary: Obese non-diabetic patients receiving semaglutide in a large randomized placebo-controlled trial lost and maintained around 15% of their body weight for over a year, potentially indicating a new era of anti-obesity drugs based on brain appetite suppression.
Article
Multidisciplinary Sciences
Chia-Yu Guh, Hong-Jhih Shen, Liv WeiChien Chen, Pei-Chen Chiu, I-Hsin Liao, Chen-Chia Lo, Yunfei Chen, Yu-Hung Hsieh, Ting-Chia Chang, Chien-Ping Yen, Yi-Yun Chen, Tom Wei-Wu Chen, Liuh-Yow Chen, Ching-Shyi Wu, Jean-Marc Egly, Hsueh-Ping Catherine Chu
Summary: This study investigates the role of Telomeric Repeat-Containing RNA (TERRA) in the Alternative Lengthening of Telomeres (ALT) mechanism. The depletion of TERRA has been shown to reduce ALT-associated PML bodies, telomere clustering, and telomere lengthening. TERRA interacts with DNA repair proteins, particularly the endonuclease XPF, to activate the DNA damage response (DDR) and induce break-induced telomere synthesis and lengthening. These findings reveal the mechanisms underlying the initiation and maintenance of ALT.
NATURE COMMUNICATIONS
(2022)
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)
Article
Multidisciplinary Sciences
Rekha Rai, Kevin Biju, Wenqi Sun, Tori Sodeinde, Amer Al-Hiysat, Jaida Morgan, Xianwen Ye, Xueqing Li, Yong Chen, Sandy Chang
Summary: This study reveals that the basic domain of TRF2 (TRF2(B)) and RAP1 cooperate to repress homology directed repair (HDR) at telomeres and prevent the formation of ultrabright telomere structures.
NATURE COMMUNICATIONS
(2023)
