Article
Virology
Sebastian O. Wendel, Avanelle Stoltz, Xuan Xu, Jazmine A. Snow, Nicholas Wallace
Summary: A subset of human papillomaviruses (HPVs), particularly HPV16, play a crucial role in the development of cervical cancer. The HPV16 E7 oncogene destabilizes RB and facilitates viral replication, while HPV16 E6 degrades p53 to mitigate replication stress. This study shows that cervical cancer cells activate the translesion synthesis (TLS) pathway to prevent replication fork collapse caused by stress. Increased expression of TLS genes is more common in cervical cancer than in other cancer types, and is associated with improved survival rates.
Review
Biochemistry & Molecular Biology
Joseph D. Kaszubowski, Michael A. Trakselis
Summary: High fidelity DNA polymerases are crucial for genome replication, but they can become stalled at damaged sites. Translesion synthesis polymerases can temporarily take over synthesis at these sites, but they are less accurate. Mechanisms are needed to recruit high fidelity polymerases back to ensure accurate synthesis.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Faye M. Vassel, Daniel J. Laverty, Ke Bian, Cortt G. Piett, Michael T. Hemann, Graham C. Walker, Zachary D. Nagel
Summary: Rev7 is a regulatory protein with multiple functions, including roles in TLS, DSB repair, replication fork protection, and cell cycle regulation. Dimerization of Rev7 is important for its roles in TLS, DSB repair, and regulation of the anaphase promoting complex, but partially dispensable for promoting mitotic spindle assembly through its interaction with Ran.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Multidisciplinary Sciences
Radhika Malik, Robert E. Johnson, Louise Prakash, Satya Prakash, Iban Ubarretxena-Belandia, Aneel K. Aggarwal
Summary: The study investigates the structure of the DNA-Pol zeta complex and its ability to extend DNA synthesis past mismatched base pairs. The results reveal the conformational changes in the Pol zeta active site and how it responds to mismatched DNA, allowing for the proper binding and extension of nucleotides. This study provides valuable insights into the regulation of DNA synthesis in eukaryotes.
NATURE COMMUNICATIONS
(2022)
Article
Developmental Biology
Gautam Chandra Sarkar, Umanshi Rautela, Anita Goyala, Sudeshna Datta, Nikhita Anand, Anupama Singh, Prachi Singh, Manish Chamoli, Arnab Mukhopadhyay
Summary: A study in Caenorhabditis elegans reveals that disruption of DNA damage response (DDR) signaling only in the uterus can cause arrested oogenesis in the pachytene stage of meiosis I when insulin/IGF-1 signaling (IIS) is low. This arrest is dependent on the transcription factor FOXO/DAF-16. Without FOXO/DAF-16, germ cells of the IIS mutant escape the arrest and produce poor-quality oocytes. Activated FOXO/DAF-16 senses DNA damage during low IIS to lower ERK/MPK-1 signaling below a threshold, promoting germ line arrest and ensuring optimal germ cell quality and progeny fitness.
Article
Cell Biology
Chu Chen, Guanhua Xu, Jiajia Chen, Chunshuai Wu, Jinlong Zhang, Jiawei Jiang, Hongxiang Hong, Zhiming Cui
Summary: This study investigated the role of transcription factor FoxO1 in facet joint osteoarthritis (FJOA) and found that FoxO1 deletion led to severe osteoarthritic changes. Transcriptome sequencing and bioinformatics analysis identified differentially expressed genes (DEGs) and potential key contributors to FJOA. Additionally, over-expression of certain genes and inhibition of others were shown to counteract the impairments caused by FoxO1 deletion in chondrocyte migration and extracellular matrix synthesis. These findings help unravel the molecular mechanisms underlying FJOA and open up promising therapeutic avenues for its treatment.
CELLULAR SIGNALLING
(2024)
Article
Microbiology
Xu Feng, Baochang Zhang, Zhe Gao, Ruyi Xu, Xiaotong Liu, Sonoko Ishino, Mingxia Feng, Yulong Shen, Yoshizumi Ishino, Qunxin She
Summary: The study reveals that Sulfolobus islandicus Dpo2, previously predicted to be inactive, is actually a functional DNA polymerase involved in translesion synthesis. Dpo2 replicates undamaged DNA with high fidelity and efficiently extends mismatched and DNA lesion-containing substrates, highlighting its importance in DNA damage repair.
Article
Microbiology
Xu Feng, Baochang Zhang, Zhe Gao, Ruyi Xu, Xiaotong Liu, Sonoko Ishino, Mingxia Feng, Yulong Shen, Yoshizumi Ishino, Qunxin She
Summary: In this work, we discovered that Sulfolobus islandicus Dpo2, a B-family DNA polymerase once predicted to be inactive, is a functional DNA polymerase involved in translesion synthesis. S. islandicus Dpo2 belongs to a large group of B-family DNA polymerases (PolB2) that exists in many archaea and some bacteria, and they carry variations in conserved amino acids in the functional domains responsible for polymerization and proofreading. Contrary to predictions, this prokaryotic B-family DNA polymerase not only replicates undamaged DNA accurately, but also efficiently extends mismatched and DNA lesion-containing substrates. Based on our findings, we propose that this enzyme functions as an extender polymerase, representing the first prokaryotic enzyme of this type. Our data also suggests that this PolB2 enzyme serves as a functional counterpart of the eukaryotic DNA polymerase Pol zeta, which is dedicated to DNA damage repair.
Article
Medicine, Research & Experimental
Tianxiang Ni, Qian Zhang, Yan Li, Caiyi Huang, Tingting Zhou, Junhao Yan, Zi-Jiang Chen
Summary: Increasing evidence suggests a close relationship between non-coding RNAs and recurrent implantation failure. Circular RNA circSTK40 plays a role in inhibiting decidualization and promoting cell survival in endometrial stromal cells, possibly through modulating the degradation of proteins such as HSP90 and CLU, leading to activation of the AKT pathway and downregulation of FOXO1 expression. Targeted treatments based on these findings could potentially benefit patients with low endometrial receptivity.
MOLECULAR THERAPY-NUCLEIC ACIDS
(2021)
Article
Biochemistry & Molecular Biology
Maria Cano-Linares, Aurora Yanez-Vilches, Nestor Garcia-Rodriguez, Marta Barrientos-Moreno, Roman Gonzalez-Prieto, Pedro San-Segundo, Helle D. Ulrich, Felix Prado
Summary: This study reveals that the HR protein Rad52 works in conjunction with the TLS machinery to repair MMS and UV light-induced ssDNA gaps. Rad52 facilitates DNA damage-induced mutagenesis and PCNA ubiquitylation through Rad51/Rad57-dependent and -independent processes, providing a novel role for recombination proteins in maintaining genome integrity.
Article
Pharmacology & Pharmacy
L. B. Volk, K. L. Cooper, T. Jiang, M. L. Paffett, L. G. Hudson
Summary: Arsenite inhibits translesion synthesis (TLS) by interfering with the function of DNA repair protein Rad18. This leads to the retention of UV-induced DNA damage and accumulation of replication stress. Arsenite also affects the activity and regulation of Rad18, inhibiting PCNA monoubiquitination and polymerase eta recruitment, thus enhancing the bypass of cyclobutane pyrimidine dimers. These effects result in increased levels of replication stress, single-stranded DNA gaps, and DNA double-strand breaks, which can potentially cause mutations and contribute to the cocarcinogenicity of arsenite.
TOXICOLOGY AND APPLIED PHARMACOLOGY
(2022)
Article
Biochemical Research Methods
Yu Wang, Dongdong Zhao, Letian Sun, Jie Wang, Liwen Fan, Guimin Cheng, Zhihui Zhang, Xiaomeng Ni, Jinhui Feng, Meng Wang, Ping Zheng, Changhao Bi, Xueli Zhang, Jibin Sun
Summary: Expanding base conversion types greatly broadens the application of base editing. The study discovered that the DNA polymerase V-mediated TLS pathway controls C-to-A editing in E. coli while C-to-G conversion is the main product in C. glutamicum. Introducing the E. coli TLS pathway into a TLS-deficient C. glutamicum mutant changes the GBE outcome from C-to-G to C-to-A. This study demonstrates the possibility of engineering TLS systems for advanced genome editing tools.
ACS SYNTHETIC BIOLOGY
(2022)
Article
Cell Biology
Huihui Ji, Zhimin Qi, Daniel Schrapel, Monika Le, Yiqiao Luo, Bin Yan, Jury Gladkich, Michael Schaefer, Li Liu, Ingrid Herr
Summary: Sulforaphane can prolong lifespan and healthspan by inducing the expression and nuclear translocation of TRA-1/GLI, and thus support healthy aging by regulating daf-16/FOXO. However, the prolonging effects of sulforaphane on lifespan and healthspan are inhibited when TRA-1 or daf-16 is interfered with by RNA interference or using worms with mutants of tra-1 or daf-16 genes.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Chemistry, Medicinal
Wenqi Wang, Xin Feng, Yu Du, Cen Liu, Xinxin Pang, Kunxiu Jiang, Xirui Wang, Yonggang Liu
Summary: By modifying pinocembrin with amino acids, the derivative pb-3 showed promising antiaging effects in increasing tolerance to thermal and oxidative stress, as well as reducing lipofuscin accumulation in Caenorhabditis elegans. The antioxidant and antiaging properties of pb-3 may involve the DAF-16/FOXO transcription process. These findings suggest that pinocembrin amino acid derivatives could be a novel agent for antiaging therapy.
DRUG DESIGN DEVELOPMENT AND THERAPY
(2021)
Article
Medicine, Research & Experimental
Xingzhuo Song, Yu Du, Cen Liu, Wei Wang, Jing Han, Xinlou Chai, Yonggang Liu
Summary: Oxidative stress disrupts redox state homeostasis and induces apoptosis. Prolonged oxidative stress can impair cell, tissue, and organ function, leading to the development of diseases. H-2 synthesized from N-Alkylamides (NAAs) of Anacyclus pyrethrum (L.) DC was investigated for its antioxidant activity and molecular mechanisms using Caenorhabditis elegans (C. elegans) and B16-F10 mouse melanoma cell models. In vivo studies on C57BL/6 mice showed the anti-vitiligo activity of H-2. The results demonstrated that H-2 increased the survival time of nematodes under oxidative stress, promoted the nuclear localization of DAF-16, and enhanced the expression of Superoxide Dismutase 3 (SOD-3) in nematodes, thus activating the antioxidant enzyme system. H-2 also reversed oxidative stress damage in the B16-F10 cell model and increased the number of melanocytes in vitiligo model mice, suggesting its potential in vitiligo treatment.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Editorial Material
Cell Biology
Jun-ichi Sakamaki, Kevin M. Ryan
DEVELOPMENTAL CELL
(2016)
Article
Biochemistry & Molecular Biology
Jun-ichi Sakamaki, Simon Wilkinson, Marcel Hahn, Nilgun Tasdemir, Jim O'Prey, William Clark, Ann Hedley, Colin Nixon, Jaclyn S. Long, Maria New, Tim Van Acker, Sharon A. Tooze, Scott W. Lowe, Ivan Dikic, Kevin M. Ryan
Review
Oncology
Maria New, Tim Van Acker, Jaclyn S. Long, Jun-ichi Sakamaki, Kevin M. Ryan, Sharon A. Tooze
FRONTIERS IN ONCOLOGY
(2017)
Article
Multidisciplinary Sciences
Pablo Sierra Gonzalez, James O'Prey, Simone Cardaci, Valentin J. A. Barthet, Jun-ichi Sakamaki, Florian Beaumatin, Antonia Roseweir, David M. Gay, Gillian Mackay, Gaurav Malviya, Elzbieta Kania, Shona Ritchie, Alice D. Baudot, Barbara Zunino, Agata Mrowinska, Colin Nixon, Darren Ennis, Aoisha Hoyle, David Millan, Iain A. McNeish, Owen J. Sansom, Joanne Edwards, Kevin M. Ryan
Article
Oncology
Maria New, Tim Van Acker, Jun-Ichi Sakamaki, Ming Jiang, Rebecca E. Saunders, Jaclyn Long, Victoria M-Y Wang, Axel Behrens, Joana Cerveira, Padhmanand Sudhakar, Tamas Korcsmaros, Harold B. J. Jefferies, Kevin M. Ryan, Michael Howell, Sharon A. Tooze
Article
Multidisciplinary Sciences
Anne-Louise Latif, Ashley Newcombe, Sha Li, Kathryn Gilroy, Neil A. Robertson, Xue Lei, Helen J. S. Stewart, John Cole, Maria Terradas Terradas, Loveena Rishi, Lynn McGarry, Claire McKeeve, Claire Reid, William Clark, Joana Campos, Kristina Kirschner, Andrew Davis, Jonathan Lopez, Jun-ichi Sakamaki, Jennifer P. Morton, Kevin M. Ryan, Stephen W. G. Tait, Sheela A. Abraham, Tessa Holyoake, Brian Higgins, Xu Huang, Karen Blyth, Mhairi Copland, Timothy J. T. Chevassut, Karen Keeshan, Peter D. Adams
Summary: The study reveals that MDM2 and BET inhibitors can synergize by stabilizing p53 protein and inhibiting BRD4-mediated suppression of p53 target genes, enhancing the therapeutic efficacy for AML treatment.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Kaito Mimura, Jun-Ichi Sakamaki, Hideaki Morishita, Masahito Kawazu, Hiroyuki Mano, Noboru Mizushima
Summary: Autophagy is a process that degrades cytoplasmic material in lysosomes and undergoes dynamic regulation in response to cellular stress. A genome-wide CRISPR screen identified a component of the de novo purine synthesis pathway as a negative regulator of autophagy. These findings suggest a potential role for nucleotide metabolism in autophagy regulation.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Biology
Caterina Iorio, Jillian L. Rourke, Lisa Wells, Jun-Ichi Sakamaki, Emily Moon, Queenie Hu, Tatsuya Kin, Robert A. Screaton
Summary: The study uses a high-throughput RNAi screen to identify the GPR3-SIK2-CDKN1B axis as key players in regulating pancreatic beta cell proliferation, suggesting that targeting GPR3 and SIK2 could stimulate beta cell regeneration in diseases like type 1 diabetes.
COMMUNICATIONS BIOLOGY
(2021)
Editorial Material
Cell Biology
Jun-Ichi Sakamaki, Noboru Mizushima
Summary: Conjugation of Atg8-family proteins to phosphatidylethanolamine (PE) is important for auto-phagosome formation. PE conjugation was previously thought to be specific to Atg8 among the ubiquitin-family proteins, but our recent study found that ubiquitin is also conjugated to PE on endosomes and the vacuole. Other ubiquitin-like proteins, like NEDD8 and ISG15, can also bind to phospholipids covalently. We propose that conjugation to phospholipids could be a common feature of the ubiquitin family.
Article
Biochemistry & Molecular Biology
Jun-ichi Sakamaki, Koji L. Ode, Yoshitaka Kurikawa, Hiroki R. Ueda, Hayashi Yamamoto, Noboru Mizushima
Summary: This study reveals that ubiquitin family proteins can conjugate to phospholipids, not only ATG8. This conjugation mainly occurs in endosomes and vacuoles and increases during starvation. In vitro experiments also demonstrate that liposomes containing ubiquitin-phospholipid can recruit specific protein components.
Article
Biochemistry & Molecular Biology
Masaru Shimasawa, Jun-ichi Sakamaki, Tatsuya Maeda, Noboru Mizushima
Summary: Cell size regulation is important for cellular functions, but the mechanisms are not fully understood. In this study, Rim21 was identified as a positive regulator of cell size through a genome-wide screen. Mutants defective in the Rim101 pathway showed consistent smaller size, while overexpression of active Rim101 increased cell size. Microscopic observation revealed changes in vacuolar and cytoplasmic volume, which were dependent on Rim21 and Rim101.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
Review
Cell Biology
Jun-ichi Sakamaki, Noboru Mizushima
Summary: The covalent attachment of ubiquitin is a common regulatory mechanism in various proteins. Recent studies have shown that ubiquitin can also be conjugated to lipids, sugars, and nucleotides. Ubiquitination of non-protein substrates can signal the recruitment of other proteins to produce specific effects.
TRENDS IN CELL BIOLOGY
(2023)
Article
Biochemical Research Methods
Jun-ichi Sakamaki, Noboru Mizushima
Summary: This article describes a method based on hydrophobicity to purify ubiquitinated phospholipids in yeast and human cells, which are then verified using phospholipase D treatment. These protocols enable the detection of both tagged and endogenous mono- and poly-ubiquitinated phospholipids by immunoblotting.
Review
Biochemistry & Molecular Biology
Jun-Ichi Sakamaki, Jaclyn S. Long, Maria New, Tim Van Acker, Sharon A. Tooze, Kevin M. Ryan
TRANSCRIPTION-AUSTIN
(2018)
