Article
Genetics & Heredity
Esther Herruzo, Estefania Sanchez-Diaz, Sara Gonzalez-Arranz, Beatriz Santos, Jesus A. Carballo, Pedro A. San-Segundo
Summary: In this study, we uncover the mechanism that Pch2 uses to travel from the nucleus to the cytoplasm, and identify a nuclear export signal in the non-catalytic domain of Pch2 required for its nucleocytoplasmic trafficking and proper checkpoint activity.
Article
Genetics & Heredity
Esther Herruzo, Ana Lago-Maciel, Sara Baztan, Beatriz Santos, Jesus A. Carballo, Pedro A. San-Segundo, Michael Lichten, Gregory P. Copenhaver, Michael Lichten, Gregory P. Copenhaver, Michael Lichten, Gregory P. Copenhaver
Summary: Studies have shown that Pch2 plays a critical role in the meiotic recombination checkpoint, supporting checkpoint activation through the cytoplasmic pool and leading to pathological consequences when accumulated in the nucleus.
Article
Multidisciplinary Sciences
Sasa Petrovic, Yvette Roske, Biria Rami, Mai Hoang Quynh Phan, Daniela Panakova, Udo Heinemann
Summary: p97 is a crucial AAA+ ATPase that extracts and unfolds substrate proteins. It contributes to various cellular processes and is regulated by adaptor proteins and posttranslational modifications (PTMs). The crystal structure of a p97:ASPL:METTL21D complex reveals how ASPL enables METTL21D to trimethylate p97 at a deeply buried lysine residue.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Chemistry, Multidisciplinary
Ziwen Jiang, Yu-Hsuan Kuo, Mengqi Zhong, Jianchao Zhang, Xin X. Zhou, Lijuan Xing, James A. Wells, Yanzhuang Wang, Michelle R. Arkin
Summary: Protein-protein interactions (PPIs) play crucial roles in cellular signaling and functions. Precise modulation of PPIs can help understand their roles in cellular events and be therapeutically valuable. In this study, an antibody fragment-based modulator for the PPI between p97 and its adaptor protein NSFL1C was developed, demonstrating its potential application in therapeutic interventions by disrupting specific intracellular PPIs.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Multidisciplinary Sciences
Inge de Krijger, Bastian Foehr, Santiago Hernandez Perez, Estelle Vincendeau, Judit Serrat, Alexander Marc Thouin, Vivek Susvirkar, Chloe Lescale, Ines Paniagua, Liesbeth Hoekman, Simranjeet Kaur, Maarten Altelaar, Ludovic Deriano, Alex C. Faesen, Jacqueline J. L. Jacobs
Summary: MAD2L2, a member of the shieldin complex, plays key roles in DNA repair by participating in shieldin assembly and function through dimerization mediated by SHLD2.
NATURE COMMUNICATIONS
(2021)
Article
Genetics & Heredity
Marina Martinez-Garcia, Pedro Robles Naharro, Marnie W. Skinner, Kerstin A. Baran, Laura I. Lascarez-Lagunas, Saravanapriah Nadarajan, Nara Shin, Carlos G. Silva-Garcia, Takamune T. Saito, Sara Beese-Sims, Brianna N. Diaz-Pacheco, Elizaveta Berson, Ana B. Castaner, Sarai Pacheco, Enrique Martinez-Perez, Philip W. Jordan, Monica P. Colaiacovo
Summary: By studying the GRAS-1 protein in C. elegans, researchers found that it plays a role in coordinating early events in meiosis by regulating the speed of chromosome movements. It is involved in the pairing of homologous chromosomes, the assembly of the synaptonemal complex, and the repair of DNA double-strand breaks.
Article
Biochemistry & Molecular Biology
Xiaoyan Wang, Lijian Shao, Kimberly K. Richardson, Wen Ling, Aaron Warren, Kimberly Krager, Nukhet Aykin-Burns, Robert Hromas, Daohong Zhou, Maria Almeida, Ha-Neui Kim
Summary: Hem1, a member of the Hem family of cytoplasmic adaptor proteins, is crucial for lymphopoiesis, innate immunity, and the transition of hematopoiesis. This study shows that Hem1 deficiency leads to increased bone mass due to defective bone resorption. Although Hem1-deficient osteoclast progenitors can differentiate into osteoclasts, fusion and bone-resorption activity are impaired, potentially due to decreased MAPK and c-Abl activity. Transplantation of wildtype hematopoietic stem and progenitor cells restores bone resorption and normalizes bone mass, highlighting the pivotal role of Hem1 in maintaining normal bone density.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Antonio Cuevas-Navarro, Richard Van, Alice Cheng, Anatoly Urisman, Pau Castel, Frank McCormick
Summary: The spindle assembly checkpoint (SAC) functions as a sensor that delays mitotic progression until proper chromosome segregation is guaranteed. Disruptions to this mechanism can lead to genomic instability and aneuploidy, which are linked to various health conditions, including cancer. Understanding the interaction between signaling pathways and the SAC can provide insights into potential therapeutic targets for conditions related to chromosomal instability.
Article
Cell Biology
Yang Wang, Tianyu Yu, Yi Han, Yazhi He, Yiran Song, Leiming Guo, Liwei An, Chunying Yang, Feng Wang
Summary: This study reveals the key regulatory role of Mad2 phosphorylation in checkpoint defects and DNA damage repair in ATM-deficient cells. ATM negatively regulates the phosphorylation of Mad2, causing decreased DNA damage repair capacity and resistance to cancer cell radiotherapy.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Xiaofang Tang, Wei Wei, John M. Snowball, Ernesto S. Nakayasu, Sheila M. Bell, Charles Ansong, Xinhua Lin, Jeffrey A. Whitsett
Summary: Eukaryotic cells go through the cell cycle to produce two daughter cells. Dys-regulation of the cell cycle can result in cell death or tumorigenesis. This study shows that EMC3, a subunit of the ER membrane complex, is a key regulator of the cell cycle. Its deficiency leads to defects in organ size and patterning, impaired cell proliferation, spindle assembly defects, chromosome mis-segregation, cell cycle arrest, and apoptosis. EMC3 works together with VCP to regulate the levels and activity of Aurora A, an essential factor for centrosome function and mitotic spindle assembly.
Article
Medicine, Research & Experimental
Taketsugu Hama, Prashanth K. B. Nagesh, Pallabita Chowdhury, Bob M. Moore, Murali M. Yallapu, Kevin R. Regner, Frank Park
Summary: The study demonstrates that thyroid receptor interacting protein 13 (TRIP13) may play a crucial role in protecting proximal tubules from DNA damage caused by cisplatin. Restoring TRIP13 activity could effectively reduce nephrotoxic damage and protect the kidney.
Article
Biochemistry & Molecular Biology
Hanchen Chen, Ting Pan, Xueao Zheng, Yongchi Huang, Chong Wu, Tongbin Yang, Shan Gao, Lili Wang, Shunping Yan
Summary: DNA replication stress is a threat to genome stability and is a characteristic feature of cancer in humans. The kinases ATR and WEE1 are essential for activating the replication stress responses. This study demonstrates that ATR-WEE1 inhibits GCN20-GCN1 activity to promote the translation of the master transcription factor, SOG1, during replication stress in Arabidopsis.
Article
Genetics & Heredity
Shuang Bai, Li Sun, Xi Wang, Shuang-Min Wang, Zhou-Qing Luo, Yamei Wang, Quan-Wen Jin
Summary: This study reveals that the timely silencing of the activated spindle assembly checkpoint (SAC) in fission yeast requires participation of the dnt1 gene. Lack of the dnt1 gene leads to increased sensitivity to thiabendazole and higher rate of lagging chromosomes. The absence of Dnt1 prolongs the inhibitory binding of mitotic checkpoint complex (MCC) to APC/C and slows down the degradation of cyclin B and securin, resulting in delayed entry into anaphase.
Article
Cell Biology
Cory Haluska, Fengzhi Jin, Yanchang Wang
Summary: This study reveals a PP2A-Swe1-CDK-Chk1-Pds1 axis that promotes recovery from DNA replication stress. The genetic data suggest the role of Swe1/CDK upstream of Pds1 in regulating anaphase entry delay in PP2A mutants. Additionally, deletion of cdc55 showed significant suppression to the viability loss of S-phase checkpoint mutants during DNA synthesis block.
MOLECULAR BIOLOGY OF THE CELL
(2021)
Article
Biochemistry & Molecular Biology
Charles H. Perry, Nathan A. Mullins, Razan B. A. Sweileh, Noha A. M. Shendy, Patrick A. Roberto, Amber L. Broadhurst, Hannah A. Nelson, Gustavo A. Miranda-Carboni, Amy N. Abell
Summary: Disruption of fetal growth has severe consequences to human health. This study identified a previously unknown role for MAP3K4 in promoting fetal and placental growth. MAP3K4 inactivation causes FGR due to placental insufficiency. The study also revealed the molecular mechanisms by which MAP3K4 promotes growth through the IGF1R/IR and Akt signaling pathway.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Review
Genetics & Heredity
Pedro A. San-Segundo, Andres Clemente-Blanco
Article
Genetics & Heredity
Laura Lascarez-Lagunas, Esther Herruzo, Alla Grishok, Pedro A. San-Segundo, Monica P. Colaiacov
Article
Cell Biology
Sara Gonzalez-Arranz, Jennifer M. Gardner, Zulin Yu, Neem J. Patel, Jonna Heldrich, Beatriz Santos, Jesus A. Carballo, Sue L. Jaspersen, Andreas Hochwagen, Pedro A. San-Segundo
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2020)
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
Biochemistry & Molecular Biology
Paula Alonso-Ramos, David Alvarez-Melo, Katerina Strouhalova, Carolina Pascual-Silva, George B. Garside, Meret Arter, Teresa Bermejo, Rokas Grigaitis, Rahel Wettstein, Marta Fernandez-Diaz, Joao Matos, Marco Geymonat, Pedro A. San-Segundo, Jesus A. Carballo
Summary: This study reveals previously undescribed functions of the evolutionary conserved Cdc14 phosphatase in the regulation of meiotic recombination, including the regulation of crossover formation and the control of the activity of the Holliday Junction resolvase Yen1/GEN1.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Genetics & Heredity
Esther Herruzo, Ana Lago-Maciel, Sara Baztan, Beatriz Santos, Jesus A. Carballo, Pedro A. San-Segundo, Michael Lichten, Gregory P. Copenhaver, Michael Lichten, Gregory P. Copenhaver, Michael Lichten, Gregory P. Copenhaver
Summary: Studies have shown that Pch2 plays a critical role in the meiotic recombination checkpoint, supporting checkpoint activation through the cytoplasmic pool and leading to pathological consequences when accumulated in the nucleus.
Article
Microbiology
A. Lechuga, D. Kazlauskas, M. Salas, M. Redrejo-Rodriguez
Summary: This study identified and characterized the DNA binding protein B35SSB from the beta-activating virus Bam35, which stimulates DNA replication in a non-specific manner. The protein contains specific residues involved in protein-ssDNA interactions and belongs to a novel group of SSBs.
FRONTIERS IN MICROBIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Ana Lechuga, Cedric Lood, Monica Berjon-Otero, Alicia del Prado, Jeroen Wagemans, Vera van Noort, Rob Lavigne, Margarita Salas, Modesto Redrejo-Rodriguez
Summary: By integrating the traditional yeast two-hybrid system and high-throughput sequencing, researchers constructed a protein-protein interaction network for the Bam35-Bacillus thuringiensis model and identified 182 high-confidence virus-host interactions. Within these interactions, host metabolism proteins and peptidases were particularly enriched, distinguishing this host-phage system from others reported in the literature.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cell Biology
Sara Gonzalez-Arranz, Isabel Acosta, Jesus A. Carballo, Beatriz Santos, Pedro A. San-Segundo
Summary: This study reveals the mechanism of polo-like kinase Cdc5 during meiotic prophase I to meiosis I transition, showing that its overexpression partially relieves the meiotic delay induced by the checkpoint. However, a mutant version lacking the N-terminal region fails to alleviate the delay. In addition, the double mutant exhibits an exacerbated meiotic block compared to the single mutant.
Article
Biochemistry & Molecular Biology
Ramya Ravindranathan, Kavya Raveendran, Frantzeskos Papanikos, Pedro A. San-Segundo, Attila Toth
Summary: The generation of haploid gametes relies on a modified version of homologous recombination in meiosis. Meiotic recombination is initiated by programmed DNA double-stranded breaks (DSBs) and involves chromosomal synapsis to enhance DSB repair. However, synapsis defects can lead to apoptosis in oocytes due to unresolved DSBs. Surprisingly, even in mutants lacking programmed DSBs, apoptosis and numerous RAD51 foci, indicative of unknown origin DSBs, were observed in SPO11-deficient oocytes. It was found that RAD51 is an unreliable marker for DSBs in oocytes, and SPO11-deficient oocytes have fewer persistent ssDNAs compared to wild-type oocytes.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Genetics & Heredity
Esther Herruzo, Estefania Sanchez-Diaz, Sara Gonzalez-Arranz, Beatriz Santos, Jesus A. Carballo, Pedro A. San-Segundo
Summary: In this study, we uncover the mechanism that Pch2 uses to travel from the nucleus to the cytoplasm, and identify a nuclear export signal in the non-catalytic domain of Pch2 required for its nucleocytoplasmic trafficking and proper checkpoint activity.