Review
Biochemistry & Molecular Biology
Hideo Tsubouchi
Summary: Homologous recombination (HR) is crucial for meiosis and is induced during meiotic prophase. The Hop2-Mnd1 complex, originally identified in budding yeast, is conserved across species and plays an essential role in meiosis. Accumulating evidence suggests that Hop2-Mnd1 promotes RecA-like recombinases for homology search and strand exchange. This review summarizes studies on the mechanism of the Hop2-Mnd1 complex in promoting HR and beyond.
Article
Developmental Biology
Yuki Takada, Ruken Yaman-Deveci, Takayuki Shirakawa, Jafar Sharif, Shin-Ichi Tomizawa, Fumihito Miura, Takashi Ito, Michio Ono, Kuniko Nakajima, Yoko Koseki, Fuyuko Shiotani, Kei-Ichiro Ishiguro, Kazuyuki Ohbo, Haruhiko Koseki
Summary: The study revealed that the essential proteins for maintenance DNA methylation, NP95 and DNMT1, are co-expressed in spermatogonia and are necessary for meiosis in male germ cells. Deficiency in Np95 or Dnmt1 in spermatocytes results in spermatogenic defects such as synaptic failure and disruption of pericentric heterochromatin clusters.
Article
Biochemistry & Molecular Biology
Wei Lee, Hiroshi Iwasaki, Hideo Tsubouchi, Hung-Wen Li
Summary: In meiosis, Dmc1 and Rad51 are responsible for pairing and exchanging strands of homologous chromosomes. The mechanisms by which Swi5-Sfr1 and Hop2-Mnd1 stimulate Dmc1-driven recombination are still unclear. Through smFRET and TPM experiments, it was found that both Hop2-Mnd1 and Swi5-Sfr1 individually enhance Dmc1 filament assembly on ssDNA, and when added together, they provide further stimulation. The binding rate of Dmc1 is enhanced by Hop2-Mnd1 while the dissociation rate is specifically reduced by Swi5-Sfr1 during nucleation.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Biology
Zhuangfeng Weng, Jiefu Zheng, Yiyi Zhou, Zuer Lu, Yixi Wu, Dongyi Xu, Huanhuan Li, Huanhuan Liang, Yingfang Liu
Summary: This study reports the structural characterization of the MCM8/9 complex using cryo-electron microscopy. The complex is arranged as a heterohexamer with a central channel for DNA binding. The N-terminal OB domains of MCM8/9 have hairpin structures that unwind duplex DNA. Activation by HROB leads to a change in symmetry and rotational motion of the C-tier ring, which is important for the unwinding ability of MCM8/9.
Article
Biology
Dorota Rousova, Vaishnavi Nivsarkar, Veronika Altmannova, Vivek B. Raina, Saskia K. Funk, David Liedtke, Petra Janning, Franziska Mueller, Heidi Reichle, Gerben Vader, John R. Weir
Summary: This study focuses on the foundational DSB factor Mer2 and reveals its interaction with nucleosomes and a chromosomal axis factor, as well as its crucial role in DSB activity. By bridging key protein complexes involved in the initiation of meiotic recombination, Mer2 is established as a keystone of the DSB machinery.
Article
Biochemistry & Molecular Biology
Monica M. Franca, Yazmine B. Condezo, Maeva Elzaiat, Natalia Felipe-Medina, Fernando Sanchez-Saez, Sergio Munoz, Raquel Sainz-Urruela, M. Rosario Martin-Hervas, Rodrigo Garcia-Valiente, Manuel A. Sanchez-Martin, Aurora Astudillo, Juan Mendez, Elena Llano, Reiner A. Veitia, Berenice B. Mendonca, Alberto M. Pendas
Summary: A homozygous RAD51B variant was identified in sisters with POI, leading to DNA repair defects and reduced crossovers. This variant also affected RAD51B interactions and replication fork progression, indicating a role in somatic genome stability maintenance.
CELL DEATH AND DIFFERENTIATION
(2022)
Article
Biochemistry & Molecular Biology
Yuliana Yosaatmadja, Hannah T. Baddock, Joseph A. Newman, Marcin Bielinski, Angeline E. Gavard, Shubhashish M. M. Mukhopadhyay, Adam A. Dannerfjord, Christopher J. Schofield, Peter J. McHugh, Opher Gileadi
Summary: Artemis is an endonuclease that plays a key role in the development of B- and T-lymphocytes and in the repair of dsDNA breaks by non-homologous end-joining. Artemis has predominantly endonuclease activity, which is different from its closely related SNM1A and SNM1B nucleases that have predominantly exonuclease activity.
NUCLEIC ACIDS RESEARCH
(2021)
Review
Cell Biology
Muwen Kong, Eric C. Greene
Summary: DNA double strand breaks are highly deleterious forms of DNA damage that, if left unrepaired, can lead to a high risk of cancer. Homologous recombination and nonhomologous end joining are the two major mechanisms responsible for repairing DSBs, and single-molecule studies have provided detailed insights into the repair processes at each step.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Jinying Wei, Guangping Meng, Jing Wu, Qiang Zhang, Jie Zhang
Summary: The study aimed to characterize key survival-specific genes for LUAD using machine learning approaches. Findings suggest that MND1 expression is associated with disease stage and overall survival in LUAD patients, indicating it as a potential diagnostic and therapeutic target for the disease.
SCIENTIFIC REPORTS
(2021)
Article
Obstetrics & Gynecology
Chunbo Xie, Weili Wang, Chaofeng Tu, Lanlan Meng, Guangxiu Lu, Ge Lin, Lin-Yu Lu, Yue-Qiu Tan
Summary: Meiosis is a crucial stage in the life cycle of sexually reproducing species, and understanding the molecular mechanisms of meiotic recombination is of great importance in comprehending the causes of human infertility and developing personalized treatments.
HUMAN REPRODUCTION UPDATE
(2022)
Article
Plant Sciences
Pablo Parra-Nunez, Nadia Fernandez-Jimenez, Miguel Pachon-Penalba, Eugenio Sanchez-Moran, Monica Pradillo, Juan Luis Santos
Summary: Mutations affecting crossover frequency and distribution during meiosis can result in aneuploid gametes and sterility. The cytogenetic consequences of colchicine-induced autotetraploids from Arabidopsis mutants with altered crossover frequency were analyzed, revealing the potential of these mutants for studying key proteins in plant meiosis.
Article
Chemistry, Multidisciplinary
Susanta Haldar, Yashu Zhang, Ying Xia, Barira Islam, Sisi Liu, Francesco L. Gervasio, Adrian J. Mulholland, Zoe A. E. Waller, Dengguo Wei, Shozeb Haider
Summary: The cationic porphyrin TMPyP4 can stabilize different topologies of DNA G4 structures via multiple binding modes, but can have both stabilizing and destabilizing effects on RNA G4 structures. The mechanism of TMPyP4-induced RNA G4 unfolding involves a two-state interaction mechanism with groove-bound and top-face-bound conformations. TMPyP4 disrupts Hoogsteen H-bonds between guanine bases and intercalates between the top-to-bottom G-tetrads, revealing a strong correlation between computational and experimental approaches.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Immunology
Anuja Singh, Tapan Behl, Aayush Sehgal, Sukhbir Singh, Neelam Sharma, Tanveer Naved, Saurabh Bhatia, Ahmed Al-Harrasi, Prasun Chakrabarti, Lotfi Aleya, Celia Vargas-De-La-Cruz, Simona Bungau
Summary: Rheumatoid arthritis is an autoimmune disease characterized by severe inflammation that damages tendons, cartilage, and bones. B cells play a significant role in the pathogenesis of RA, and targeting B cells has shown therapeutic efficacy in treating autoantibody-related conditions, including RA. The development of B-cell-targeted therapies has led to a better understanding of the diverse roles of B cells in autoimmune diseases and their potential as effective treatment targets.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2021)
Article
Plant Sciences
Guilherme T. Braz, Fan Yu, Hainan Zhao, Zuhu Deng, James A. Birchler, Jiming Jiang
Summary: The DNA sequence variation among homoeologous chromosomes contributes to the diploidization process of allopolyploids, favoring the establishment of exclusive homologous chromosome pairing.
Review
Biochemistry & Molecular Biology
Fan Zhang, Zhiwei Huang
Summary: This article reviews the structure and biochemical mechanisms of versatile effector proteins from class II CRISPR-Cas systems, studying their target specificity, PAM restriction, and activity regulation, and discussing strategies to improve genome engineering tools.
TRENDS IN BIOCHEMICAL SCIENCES
(2022)
Article
Genetics & Heredity
Mengling Qi, Peter D. Stenson, Edward Ball, John A. Tainer, Albino Bacolla, Hildegard Kehrer-Sawatzki, David N. Cooper, Huiying Zhao
Summary: Microdeletions and gross deletions are important causes of human inherited disease, and their genomic locations are influenced by the DNA sequence environment. This study analyzed the DNA sequences near breakpoint junctions and found correlations between the frequencies of non-B DNA-forming repeats, GC-content, specific sequence motifs, and deletion length. The study also proposed using a deletion length cut-off of 25-30 bp to functionally distinguish microdeletions from gross deletions.
Review
Biochemistry & Molecular Biology
Samuel R. Witus, Weixing Zhao, Peter S. Brzovic, Rachel E. Klevit
Summary: Mutations in BRCA1 and BARD1 predispose carriers to breast and ovarian cancers. Recent advancements in structural and cellular biology have provided critical insights into how BRCA1/BARD1 serves as a nucleosome reader and writer, facilitating transcriptional regulation and DNA repair.
TRENDS IN BIOCHEMICAL SCIENCES
(2022)
Article
Oncology
Xiangliang Yuan, Yimin Duan, Yi Xiao, Kai Sun, Yutao Qi, Yuan Zhang, Zamal Ahmed, Davide Moiani, Jun Yao, Hongzhong Li, Lin Zhang, Arseniy E. Yuzhalin, Ping Li, Chenyu Zhang, Akosua Badu-Nkansah, Yohei Saito, Xianghua Liu, Wen-Ling Kuo, Haoqiang Ying, Shao-Cong Sun, Jenny C. Chang, John A. Tainer, Dihua Yu
Summary: The study found that vitamin E has a significant impact on the survival rate of patients treated with immune checkpoint therapy, enhancing the efficacy of ICT and promoting antigen presentation by inhibiting SHP1 to activate anti-tumor T-cell immunity.
Article
Cell Biology
Alexandra Berroyer, Albino Bacolla, John A. Tainer, Nayun Kim
Summary: Top1 plays a critical role in maintaining stability at G4-forming genomic loci, and its inhibition by anticancer drugs can lead to increased genomic instability. CPT-resistant Top1 mutants enhance G4-induced recombination and synergize with Nsr1 to exacerbate genomic instability, complicating patient treatment.
Article
Multidisciplinary Sciences
Nicholas P. D. Liau, Matthew C. Johnson, Saeed Izadi, Luca Gerosa, Michal Hammel, John M. Bruning, Timothy J. Wendorff, Wilson Phung, Sarah G. Hymowitz, Jawahar Sudhamsu
Summary: The RAS-RAF pathway is commonly dysregulated in human cancers, and the mechanisms underlying RAF activation have been poorly understood. This study presents the cryo-electron microscopy structure of the SHOC2-PP1C-MRAS complex, revealing the molecular architecture and the dependence of RAS isoforms for complex formation. The findings shed light on the specificity of PP1C for RAF activation and provide insights for targeting this pathway with new inhibitors.
Article
Multidisciplinary Sciences
Reliza J. McGinnis, Chad A. Brambley, Brandon Stamey, William C. Green, Kimberly N. Gragg, Erin R. Cafferty, Thomas C. Terwilliger, Michal Hammel, Thomas J. Hollis, Justin M. Miller, Maria D. Gainey, Jamie R. Wallen
Summary: In this study, the X-ray crystal structure of a bacteriophage immunity repressor bound to DNA was determined. The repressor was found to bind an asymmetric DNA sequence using two independent DNA binding domains. The structure was supported by various experiments and a model for the regulation of transcription initiation and elongation by dual DNA binding domains was proposed.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Vincent Blay, Saule Gailiunaite, Chih-Ying Lee, Hao-Yen Chang, Douglas R. Houston, Ted Hupp, Peter Chi
Summary: In this study, we explore various ATPases to find attractive binding pockets for drug discovery. Through computational design, we identified two novel inhibitors against RAD51, a promising target in cancer treatment.
BIOORGANIC & MEDICINAL CHEMISTRY
(2022)
Article
Multidisciplinary Sciences
Albert K. Liu, Jose H. Pereira, Alexander J. Kehl, Daniel J. Rosenberg, Douglas J. Orr, Simon K. S. Chu, Douglas M. Banda, Michal Hammel, Paul D. Adams, Justin B. Siegel, Patrick M. Shih
Summary: Oligomerization is a core structural feature of many proteins, but there is a lack of diversity-driven structural studies on the evolutionary trajectory of these assemblies. This study reveals the evolutionary history of RuBisCOs and discovers a new tetrameric RuBisCO, demonstrating how structural plasticity gives rise to new oligomeric states.
Article
Biochemistry & Molecular Biology
Amer Bralic, Muhammad Tehseen, Mohamed A. Sobhy, Chi-Lin Tsai, Lubna Alhudhali, Gang Yi, Jina Yu, Chunli Yan, Ivaylo Ivanov, Susan E. Tsutakawa, John A. Tainer, Samir M. Hamdan
Summary: Nucleotide excision repair (NER) is crucial for removing bulky DNA lesions, and this study reveals that the XPG nuclease plays a dual role in lesion recognition and excision. XPG stimulates TFIIH-dependent dsDNA unwinding and cleavage activity, and this coordination requires a DNA bubble longer than 15 nucleotides.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Biology
Wei-Jiun Tsai, Yi-Hsin Lai, Yong-An Shi, Michal Hammel, Anthony P. Duff, Andrew E. Whitten, Karyn L. Wilde, Chun-Ming Wu, Robert Knott, U-Ser Jeng, Chia-Yu Kang, Chih-Yu Hsu, Jian-Li Wu, Pei-Jane Tsai, Chuan Chiang-Ni, Jiunn-Jong Wu, Yee-Shin Lin, Ching-Chuan Liu, Toshiya Senda, Shuying Wang
Summary: The structure and dynamic nature of the NADase/SLO complex in Group A Streptococcus (GAS) have been elucidated, revealing atomic details of the complex interface and functionally relevant conformations. The salt-bridge interaction between NADase and SLO is found to be important for the cytotoxicity and resistance to phagocytic killing during GAS infection. In a murine infection model, the biological significance of the NADase/SLO complex in GAS virulence is demonstrated.
COMMUNICATIONS BIOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Michal Hammel, Yuchen Fan, Apoorva Sarode, Amy E. Byrnes, Nanzhi Zang, Ponien Kou, Karthik Nagapudi, Dennis Leung, Casper C. Hoogenraad, Tao Chen, Chun-Wan Yen, Greg L. Hura
Summary: Using a high-throughput screening method combined with structural analysis and gene silencing assessment, we found that PEG-lipids can modify the core organization of ASO-loaded LNPs, affecting their gene silencing activity.
Article
Biochemistry & Molecular Biology
Samuel R. Witus, Lisa M. Tuttle, Wenjing Li, Alex Zelter, Meiling Wang, Klaiten E. Kermoade, Damien B. Wilburn, Trisha N. Davis, Peter S. Brzovic, Weixing Zhao, Rachel E. Klevit
Summary: BRCA1/BARD1 is a tumor suppressor gene with functions in DNA damage repair and transcriptional regulation. It interacts with nucleosomes and facilitates ubiquitylation of histone H2A. Our study reveals novel interactions involving an intrinsically disordered DNA-binding region of BARD1 that support H2A ubiquitylation and recruitment to chromatin and DNA damage sites. These interactions contribute to cell survival and identify a network of BARD1-nucleosome interactions on chromatin.
Article
Biochemistry & Molecular Biology
Chia-Chun Liu, Hsin-Ru Chan, Guan-Chin Su, Yan-Zhu Hsieh, Kai-Hang Lei, Tomoka Kato, Tai-Yuan Yu, Yu-wen Kao, Tzu-Hao Cheng, Peter Chi, Jing-Jer Lin
Summary: The non-coding RNA TERRA regulates telomere recombination. Mutations in DNA2, EXO1, MRE11, and SAE2 cause delay in type II survivor formation, while mutation in RAD27 results in early formation of type II recombination. Rad27 cleaves TERRA in the context of an R-loop or flapped RNA-DNA duplex and regulates C-circles during telomere recombination.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Chia-Lun Guh, Kai-Hang Lei, Yi-An Chen, Yi-Zhen Jiang, Hao-Yen Chang, Hungjiun Liaw, Hung-Wen Li, Hsin-Yung Yen, Peter Chi
Summary: This study provides evidence for an unknown function of RAD51 paralogs in synergizing with RAD51 nucleoprotein filament to prevent degradation of stressed replication forks.
NUCLEIC ACIDS RESEARCH
(2023)
Review
Biochemistry & Molecular Biology
Atanu Mondal, Apoorva Bhattacharya, Vipin Singh, Shruti Pandita, Albino Bacolla, Raj K. Pandita, John A. Tainer, Kenneth S. Ramos, Tej K. Pandita, Chandrima Das
Summary: From initiation to progression, cancer cells experience a variety of internal and external stresses, leading to changes in their epigenome and transcriptome. Understanding the stress response pathways of cancer cells is crucial for developing novel anticancer therapies.
MOLECULAR AND CELLULAR BIOLOGY
(2022)
