Review
Cell Biology
Stephanie M. Ackerson, Carlan Romney, P. Logan Schuck, Jason A. Stewart
Summary: Regulation of DNA double-strand breaks and telomeres in cells is diametrically opposed, with DSBs requiring quick recognition and repair while telomeres must be protected to prevent unwanted chromosome fusions. Decision on whether to join DNA ends is critical for genome stability, and processing of telomeres and DSBs share commonalities. Repair of DSBs is determined by decision points that shift towards homologous recombination (HR) or non-homologous end joining (NHEJ).
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Oncology
Kailong Hou, Yuyang Yu, Duda Li, Yanduo Zhang, Ke Zhang, Jinkai Tong, Kunxian Yang, Shuting Jia
Summary: This article reviews the mechanisms and processes of alternative lengthening of telomeres (ALT), and identifies ALT as a potential valuable drug target for clinical telomerase-negative tumor treatment.
Article
Biochemistry & Molecular Biology
Gaelle Pennarun, Julien Picotto, Laure Etourneaud, Anna-Rita Redavid, Anais Certain, Laurent R. Gauthier, Paula Fontanilla-Ramirez, Didier Busso, Caroline Chabance-Okumura, Benoit Theze, Francois D. Boussin, Pascale Bertrand
Summary: The study reveals that overexpression of lamin B1 disrupts the shelterin complex, leading to telomere instability, telomeric fusions, and telomere losses in human cells. Additionally, new interactions between lamin B1 and shelterin proteins may play a crucial role in telomere stability.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Gaelle Pennarun, Julien Picotto, Laure Etourneaud, Anna-Rita Redavid, Anais Certain, Laurent R. Gauthier, Paula Fontanilla-Ramirez, Didier Busso, Caroline Chabance-Okumura, Benoit Theze, Francois D. Boussin, Pascale Bertrand
Summary: Overexpression of lamin B1 disrupts the shelterin complex, leading to telomere instability and aberrations in human cells. This dysregulation is associated with mislocalization of TRF2, and the interaction between lamin B1 and TRF2 at the nuclear periphery may play a role in telomere stability.
NUCLEIC ACIDS RESEARCH
(2021)
Review
Cell Biology
Rita Valador Fernandes, Marianna Feretzaki, Joachim Lingner
Summary: Telomeres play a crucial role in protecting chromosome ends and maintaining their integrity through mechanisms such as semiconservative DNA replication, telomerase, and homologous recombination. The long noncoding RNA TERRA is involved in modulating telomeric chromatin structure and checkpoint signaling, particularly in response to damaged or short telomeres. R-loop formation and its regulation by shelterin proteins can impact telomere maintenance by DNA recombination, potentially influencing telomere replication in normal cells and ALT cancer cells.
Article
Cell Biology
Chia-Wei Yang, Meng-Hsun Hsieh, Hao-Jhe Sun, Shu-Chun Teng
Summary: Telomere-nuclear envelope association may inhibit telomere-telomere recombination, with SUN1 depletion stimulating the formation of alternative lengthening of telomeres-associated promyelocytic leukemia bodies in ALT cells, while overexpression of the RAP1-SUN1 chimera protein suppresses APB formation.
Article
Biochemistry & Molecular Biology
Dheva Setiaputra, Cristina Escribano-Diaz, Julia K. Reinert, Pooja Sadana, Dali Zong, Elsa Callen, Cherine Sifri, Jan Seebacher, Andre Nussenzweig, Nicolas H. Thoma, Daniel Durocher
Summary: The chromatin-binding protein 53BP1 promotes DNA repair by recruiting downstream effectors such as PTIP, RIF1, and shieldin to DNA double-strand break sites. This study reveals that RIF1 is a phosphopeptide-binding protein that directly interacts with three phosphorylated epitopes on 53BP1. The recruitment of RIF1 and an alternative mode of shieldin to DNA-damage sites, which is dependent on RIF1 but does not require its interaction with 53BP1, are both essential for efficient DNA repair.
Article
Biochemistry & Molecular Biology
Sijie Liu, Yu Hua, Jingna Wang, Lingyan Li, Junjie Yuan, Bo Zhang, Ziyang Wang, Jianguo Ji, Daochun Kong
Summary: Protection of 30 overhangs in DNA double-strand breaks (DSBs) repair is achieved through the transient formation of RNA-DNA hybrids, with RNA polymerase III (RNAPIII) responsible for synthesizing the RNA strand. CtIP and MRN nuclease activity are required for initiating RNAPIII-mediated RNA synthesis at DSBs. Reduced RNAPIII levels suppress homologous recombination (HR) and lead to genetic loss > 30 bp at DSBs.
Article
Biochemistry & Molecular Biology
Mitsunori Higa, Yukihiro Matsuda, Jumpei Fujii, Nozomi Sugimoto, Kazumasa Yoshida, Masatoshi Fujita
Summary: TRF2-mediated recruitment of ORC contributes to the suppression of telomere instability, while the biological significance of the TRF2-ORC interaction for telomere maintenance remains largely elusive.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Biology
Kentaro Nakashima, Yuya Kunisaki, Kentaro Hosokawa, Kazuhito Gotoh, Hisayuki Yao, Ryosuke Yuta, Yuichiro Semba, Jumpei Nogami, Yoshikane Kikushige, Patrick S. Stumpf, Ben D. MacArthur, Dongchon Kang, Koichi Akashi, Shouichi Ohga, Fumio Arai
Summary: Protection of telomeres 1a (POT1a) is crucial for maintaining the stability of the bone marrow microenvironment and supporting B-lymphopoiesis. Deletion of POT1a in mesenchymal stem cells (MSCs) may lead to bone marrow dysfunction and myeloid skewing.
COMMUNICATIONS BIOLOGY
(2023)
Article
Cell Biology
Xiaocui Li, Xiaojuan Li, Chen Xie, Sihui Cai, Mengqiu Li, Heping Jin, Shu Wu, Jun Cui, Haiying Liu, Yong Zhao
Summary: cGAS acts as a key regulator in inhibiting mitotic DNA double-strand break repair and protecting short telomeres from end-to-end fusion independent of the canonical cGAS-STING pathway. Depletion of cGAS leads to mitotic chromosome end-to-end fusions predominantly occurring between short telomeres, demonstrating its role in genome stability and replicative senescence.
Article
Biochemical Research Methods
Rajula Elango, Arvind Panday, Nicholas A. Willis, Ralph Scully
Summary: In this study, CRISPR/Cas9 was employed to generate large deletions in the coding region of a gene of interest, producing a hemizygous cell line. Precise in-frame deletions were then engineered within the intact wild type allele, enabling the study of multi-domain proteins. The optimized protocol allowed for efficient screening of effective sgRNA pairs and the engineering of either in-frame deletions or frameshift mutations in mouse embryonic stem cells.
Article
Multidisciplinary Sciences
Jiuer Liu, Feng-Zhu Wang, Chong Li, Yujia Li, Jian-Feng Li
Summary: TAGs constitute a significant portion of plant genomes and the multiplex CRISPR system is commonly used for targeted TAG deletions. However, it has been discovered that a large percentage of CRISPR-mediated TAG knockout alleles are actually delinver bi-alleles, which are commonly misidentified as homozygous deletion alleles. This misunderstanding can lead to incorrect interpretation of experimental data and the production of genetically heterogeneous progenies. Delinver mutations are primarily correlated with deletion frequencies, rather than chromosomal locations or deletion sizes, and can also occur at non-TAG loci during multiplexed CRISPR editing.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Jiaci Li, Yaqing Jing, Yi Liu, Yawei Ru, Mingyan Ju, Yuxia Zhao, Guang Li
Summary: The study revealed abundant copy number variations, large chromosomal deletions, and impaired HR repair in PCB153-exposed HEK293T cells. The RNA-seq data confirmed the suppression of HR repairing genes by PCB153 poisoning. These findings provide new insight into the genotoxicity of PCB153 and suggest a need for further research on its toxic effects in the human body.
Article
Multidisciplinary Sciences
Hyung Jun Kim, Chenshu Liu, Liangyu Zhang, Abby F. Dernburg
Summary: Interactions between chromosomes and LINC complexes in the nuclear envelope play a critical role in promoting homolog pairing and synapsis during meiosis. MJL-1, a meiosis-specific NE protein, is essential for these interactions in C. elegans. Disruption of MJL-1 results in impaired chromosome movements, nonhomologous synapsis, and defective homolog pairing during meiosis. The similarities in the molecular architecture of meiotic chromosome-NE attachments across different organisms suggest a common origin and/or function of this structure.
Article
Biochemistry & Molecular Biology
Yanjing Li, Lijie Zhao, Xiaoxu Tian, Chao Peng, Fan Gong, Yong Chen
Article
Multidisciplinary Sciences
Guochao Chen, Duo Wang, Bin Wu, Fuxiang Yan, Hongjuan Xue, Quanmeng Wang, Shu Quan, Yong Chen
NATURE COMMUNICATIONS
(2020)
Article
Multidisciplinary Sciences
Alessandro Cicconi, Rekha Rai, Xuexue Xiong, Cayla Broton, Amer Al-Hiyasat, Chunyi Hu, Siying Dong, Wenqi Sun, Jennifer Garbarino, Ranjit S. Bindra, Carl Schildkraut, Yong Chen, Sandy Chang
NATURE COMMUNICATIONS
(2020)
Article
Genetics & Heredity
Hyoju Ban, Wenqi Sun, Yu-Hang Chen, Yong Chen, Fei Li
Summary: This study reveals the important role of the RNA-binding protein Dri1 in the assembly of heterochromatin through its interaction with the RNAi pathway and histone deacetylases (HDACs). Dri1 is involved in recruiting proteins essential for heterochromatin formation and maintenance, highlighting its significance in regulating gene expression and genome stability.
Article
Biochemistry & Molecular Biology
Yongxin Zheng, Yinping Huang, Jun Mencius, Yanjing Li, Lijie Zhao, Wanting Luo, Yong Chen, Shu Quan
Summary: MLL3 and MLL4 utilize distinct kinetic mechanisms in catalyzing the monomethylation of histone H3 lysine 4, which may provide insights into their differential functions.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Multidisciplinary Sciences
Peili Gu, Shuting Jia, Taylor Takasugi, Valerie M. Tesmer, Jayakrishnan Nandakumar, Yong Chen, Sandy Chang
Summary: The human shelterin proteins POT1 and TPP1 form a stable heterodimer that protects telomere ends. Two functionally distinct POT1 proteins in mice have been identified, with POT1b enhancing telomerase recruitment to telomeres and coordinating the synthesis of telomeric G- and C-strands, while POT1a negatively regulates telomere length by inhibiting telomerase recruitment. The discovery of unique amino acids between POT1a and POT1b sheds light on the mechanistic basis for their different functions in regulating telomeres.
NATURE COMMUNICATIONS
(2021)
Correction
Biochemistry & Molecular Biology
Chunyi Hu, Haruna Inoue, Wenqi Sun, Yumiko Takeshita, Yaoguang Huang, Ying Xu, Junko Kanoh, Yong Chen
NUCLEIC ACIDS RESEARCH
(2021)
Article
Multidisciplinary Sciences
Duo Wang, Fuxiang Yan, Ping Wu, Kexue Ge, Muchun Li, Tingting Li, Ying Gao, Chao Peng, Yong Chen
Summary: This study delves into the histone modification of lysine benzoylation (Kbz) in yeast, characterizing the proteins involved in writing, erasing, and reading Kbz marks. Additionally, non-histone proteins bearing Kbz are identified, providing insights into the roles of Kbz in various cellular processes.
NATURE COMMUNICATIONS
(2022)
Review
Cell Biology
Yanjing Li, Kexue Ge, Tingting Li, Run Cai, Yong Chen
Summary: This review highlights the recent progress in structural studies of histone lysine methyltransferases (HKMTs), which play important roles in regulating chromatin structure and gene expression. The focus is on representative HKMTs (H3K4, H3K27, H3K36, H3K79, and H4K20 methyltransferases) in complex with nucleosomes, with emphasis on understanding the molecular mechanisms of nucleosome recognition and trans-histone crosstalk by these enzymes. These structural studies shed light on the roles of HKMTs in tumorigenesis and provide a basis for developing novel therapeutic approaches targeting HKMTs in cancer.
Article
Multidisciplinary Sciences
Lijie Zhao, Naizhe Huang, Jun Mencius, Yanjing Li, Ying Xu, Yongxin Zheng, Wei He, Na Li, Jun Zheng, Min Zhuang, Shu Quan, Yong Chen
Summary: In this study, two key mechanisms of DPY30 in regulating MLL1 activity were revealed: a nucleosome-independent mechanism and a nucleosome-specific mechanism. DPY30 stabilizes ASH2L to increase the stability and interactions of the MLL1 complex, promoting its compaction and stabilization and enhancing its activity on substrates. Additionally, DPY30-stabilized ASH2L acquires additional interfaces with H3 and nucleosomal DNA, boosting the methyltransferase activity of the MLL1 complex on nucleosomes.
Article
Biochemistry & Molecular Biology
Yanjing Li, Lijie Zhao, Yuebin Zhang, Ping Wu, Ying Xu, Jun Mencius, Yongxin Zheng, Xiaoman Wang, Wancheng Xu, Naizhe Huang, Xianwen Ye, Ming Lei, Pan Shi, Changlin Tian, Chao Peng, Guohui Li, Zhijun Liu, Shu Quan, Yong Chen
Summary: This study develops methodologies to measure the methylation rate difference between different states of methylation and demonstrates that MLL proteins possess distinct product specificities. Structural analyses reveal that the dynamics of conserved tyrosine residues fine-tune the product specificity, and the variation in intramolecular interaction affects the dynamics, determining the product specificities of MLL proteins.
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)
Letter
Cell Biology
Naijin Zhang, Ying Zhang, Yong Chen, Hao Qian, Boquan Wu, Saien Lu, Shilong You, Wancheng Xu, Yuanming Zou, Xinyue Huang, Wenbin Wang, Jingwei Liu, Da Li, Liu Cao, Yingxian Sun
Article
Biochemistry & Molecular Biology
Minh Chau Nguyen, Duo Wang, Brianna J. Klein, Yong Chen, Tatiana G. Kutateladze
Summary: We investigate the association of Taf14 with other subunits of essential complexes and describe the mechanisms and factors that affect this association. Our findings provide insights into how Taf14 is distributed among the complexes.
BIOCHIMICA ET BIOPHYSICA ACTA-GENE REGULATORY MECHANISMS
(2023)
Article
Cell Biology
Min Chen, Kangjunjie Wang, Ying Han, Shukun Yan, Huairui Yuan, Qiuli Liu, Long Li, Ni Li, Hongwen Zhu, Dayun Lu, Kaihua Wang, Fen Liu, Dakui Luo, Yuxue Zhang, Jun Jiang, Dali Li, Lei Zhang, Hongbin Ji, Hu Zhou, Yong Chen, Jun Qin, Daming Gao
Summary: AKT kinase plays a crucial role in cell metabolism and survival, and its activation is strictly regulated. We have identified XAF1 as a direct interacting protein of AKT1, which binds to the N-terminal region of AKT1 to block its activation. XAF1 knockout leads to AKT activation in mouse muscle and fat tissues and reduces body weight gain and insulin resistance induced by high-fat diet.