Review
Biochemistry & Molecular Biology
Jung Min Kim
Summary: Microtubules are key components of the cytoskeleton and play important roles in cellular processes and genome maintenance. This review highlights recent advances in understanding the role of microtubule dynamics in DNA damage response and repair.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Endocrinology & Metabolism
Yunfeng Bai, Cuiting Wei, Ping Li, Xuefeng Sun, Guangyan Cai, Xiangmei Chen, Quan Hong
Summary: The primary cilium is crucial for kidney development and maintaining renal function. Defects in cilia structure and function are associated with the progression of renal diseases.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Review
Cell Biology
Ruixin Ge, Minghui Cao, Miao Chen, Min Liu, Songbo Xie
Summary: Primary cilia function as sensory organelles that monitor extracellular signals and transduce them into intracellular responses. Actin and microtubule networks play critical roles in primary ciliogenesis and maintenance. Targeting cytoskeleton-associated proteins may be a promising therapeutic strategy for treating ciliopathies.
JOURNAL OF CELLULAR PHYSIOLOGY
(2022)
Article
Cell Biology
Ezgi Odabasi, Deniz Conkar, Jovana Deretic, Umut Batman, Kari-Anne M. Frikstad, Sebastian Patzke, Elif Nur Firat-Karalar
Summary: CCDC66 is a microtubule-associated protein involved in cilium biogenesis and ciliopathies. It localizes between centrosomes, centriolar satellites, and the ciliary axoneme and tip during cilium biogenesis. Depletion of CCDC66 leads to defects in cilium assembly, length, and morphology, as well as impaired Hedgehog pathway activation. Furthermore, CCDC66 is necessary for the recruitment of transition zone proteins and intraflagellar transport B (IFT-B) machinery to the basal body. Overall, CCDC66 plays a multifaceted role in regulating the primary cilium and provides insight into the assembly of functional cilia.
JOURNAL OF CELL SCIENCE
(2023)
Article
Biochemistry & Molecular Biology
Le P. Ngo, Simran Kaushal, A. Isaac Chaim, Patrizia Mazzucato, Catherine Ricciardi, D. Leona Samson, D. Zachary Nagel, P. Bevin Engelward
Summary: By utilizing the CometChip, researchers uncovered significant variability in DNA repair efficiency among individuals, indicating its potential utility in future epidemiological and clinical studies.
FREE RADICAL BIOLOGY AND MEDICINE
(2021)
Review
Biochemistry & Molecular Biology
Yu-Young Tsai, Chun-Hao Su, Woan-Yuh Tarn
Summary: The tumor suppressor gene p53 plays a critical role in preventing tumor progression, but inappropriate activation of p53 can lead to various human inherited disorders. Genes related to these disorders are involved in transcriptional regulation, DNA damage-repair pathways, and other cellular processes, which may result in excessive p53 activation and developmental defects. Mouse models have shown that inactivation of p53 can alleviate disorder-related phenotypes, and potential therapeutic strategies for genetic disorders associated with p53 misactivation are being discussed.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Cell Biology
Kerstin Hasenpusch-Theil, Thomas Theil
Summary: The formation of the cerebral cortex, a complex process involving various types of neurons and complex connections, is crucial for advanced neural functions. Recent studies have linked cilia to processes such as neurogenesis and neuronal migration during cortex development.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Ting-Yu Chen, Bu-Miin Huang, Tang K. Tang, Yu-Ying Chao, Xiao-Yi Xiao, Pei-Rong Lee, Li-Yun Yang, Chia-Yih Wang
Summary: The DNA-PK-p53 cascade induces primary cilia formation under genotoxic stress, contributing to the DNA damage response, while lack of this pathway decreases genotoxic stress-induced ciliogenesis. Besides, ciliogenesis is regulated not only by DNA-PK, but also by autophagy.
CELL DEATH AND DIFFERENTIATION
(2021)
Article
Biochemistry & Molecular Biology
Fatmanur Tiryaki, Jovana Deretic, Elif Nur Firat-Karalar
Summary: Centrioles and cilia are essential microtubule-based structures in cells that play critical roles in cell function and development. This study identifies a new microtubule-associated protein, ENKD1, which regulates microtubule organization and stability. Furthermore, it shows that ENKD1 depletion leads to defective regulation of ciliary length and content, as well as a failure to respond to Hedgehog pathway activation.
Article
Biology
Andre Bras Goncalves, Sarah Kirstine Hasselbalch, Beinta Biskopsto Joensen, Sebastian Patzke, Pernille Martens, Signe Krogh Ohlsen, Mathieu Quinodoz, Konstantinos Nikopoulos, Reem Suleiman, Magnus Per Damso Jeppesen, Catja Weiss, Soren Tvorup Christensen, Carlo Rivolta, Jens S. Andersen, Pietro Farinelli, Lotte Bang Pedersen
Summary: CEP78 is a centrosomal protein involved in ciliogenesis and ciliary length control. Through interaction with other proteins like CEP350 and EDD1, CEP78 negatively regulates CP110 level to promote ciliogenesis downstream of CEP350. This discovery provides important insights into the role of CEP78 in cellular ciliogenesis.
Article
Immunology
Kerstin Felgentreff, Ulrich Baumann, Christian Klemann, Catharina Schuetz, Dorothee Viemann, Martin Wetzke, Ulrich Pannicke, Sandra von Hardenberg, Bernd Auber, Klaus-Michael Debatin, Eva-Maria Jacobsen, Manfred Hoenig, Ansgar Schulz, Klaus Schwarz
Summary: DNA damage is a common event in every cell, and proteins of the DNA damage response network play a crucial role in sensing and repairing DNA lesions. Genetic defects in DNA repair proteins can lead to immunodeficiency, bone marrow failure syndromes, and increased cancer susceptibility. DDR biomarkers are useful for diagnosing NHEJ defects and AT, with some limitations depending on the specific DNA repair deficiency.
JOURNAL OF CLINICAL IMMUNOLOGY
(2022)
Article
Oncology
Catherine M. Nickson, Maria Rita Fabbrizi, Rachel J. Carter, Jonathan R. Hughes, Andrzej Kacperek, Mark A. Hill, Jason L. Parsons
Summary: Ionizing radiation induces DNA damage leading to cell death. The biological effects of high-LET IR are not well understood, but USP9X plays a crucial role in cell survival post high-LET radiation by stabilizing proteins involved in centrosome formation.
FRONTIERS IN ONCOLOGY
(2021)
Review
Cell Biology
Leticia Labat-de-Hoz, Armando Rubio-Ramos, Javier Casares-Arias, Miguel Bernabe-Rubio, Isabel Correas, Miguel A. Alonso
Summary: Primary cilia are microtubule-based protrusions surrounded by a ciliary membrane equipped with selected receptors that control important signaling pathways in cell growth and development. This review presents a model of primary ciliogenesis by an alternative route involving the midbody remnant from cytokinesis, which delivers membranes to the centrosome for ciliary membrane assembly. The involvement of the midbody remnant in primary cilium formation and its regulation by the ESCRT machinery are discussed, along with the emerging roles of membrane compartmentalization.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Dana Jurkovicova, Christiana M. Neophytou, Ana Cipak Gasparovic, Ana Cristina Goncalves
Summary: Resistance to chemo- and radiotherapy is a common occurrence in cancer patients, necessitating the continuous investigation and development of new cancer therapies. The DNA damage response (DDR) plays a crucial role in maintaining genomic stability, but defects in DDR machinery are associated with different types of cancers. Current developments include the use of poly (ADP-ribose) polymerase inhibitors (PARP inhibitors) as DDR inhibitors (DDRi) for various cancers. However, resistance to DDRi, including PARP inhibitors, is becoming a growing concern in clinical settings. This review highlights the importance of DDR pathways in cancer therapy, its role in treatment resistance, and its potential for anticancer treatment.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Obstetrics & Gynecology
Kashmira Bane, Junita Desouza, Diksha Shetty, Prakash Choudhary, Shalaka Kadam, R. R. Katkam, Gwendolyn Fernandes, Raj Sawant, Uddhavraj Dudhedia, Neeta Warty, Anahita Chauhan, Uddhav Chaudhari, Rahul Gajbhiye, Geetanjali Sachdeva
Summary: The study indicates that the DNA damage response is dysregulated in the eutopic endometrium of women with endometriosis, with higher expression of DDR genes compared to those without the disease. Additionally, DNA repair genes are also up-regulated in the eutopic endometrium of women with endometriosis.
HUMAN REPRODUCTION
(2021)
Article
Polymer Science
Anna P. Constantinou, Valeria Nele, James J. Doutch, Joana S. Correia, Roman Moiseev, Martina Cihova, David C. A. Gaboriau, Jonathan Krell, Vitaliy V. Khutoryanskiy, Molly M. Stevens, Theoni K. Georgiou
Summary: In this study, thermoresponsive polymers and their gelling behavior are investigated. A cost-effective biocompatible alternative to commercially available polymers is reported, which forms gels at low concentrations. The differences in gelling mechanisms between the investigated polymer and Poloxamer P407 (Pluronic F127) are elucidated through nanoscale self-assembly and rheological analysis.
Editorial Material
Biochemistry & Molecular Biology
Ciaran G. Morrison
Summary: In this study, the co-crystallized structures revealed the molecular mechanism of CEP164 recruiting TTBK2 to the distal end of centrioles and how ciliopathy mutations in CEP164 disrupt the CEP164-TTBK2 complex.
Article
Microbiology
Sabrina Yahiya, Sarah Jordan, Holly X. Smith, David C. A. Gaboriau, Mufuliat T. Famodimu, Farah A. Dahalan, Alisje Churchyard, George W. Ashdown, Jake Baum
Summary: Formation of gametes in the malaria parasite occurs in the midgut of the mosquito and is critical to parasite transmission. A new live-cell fluorescence imaging workflow has been developed to capture the entire process of microgametogenesis, showing the rapid and complex cellular transformation involved.
Article
Anatomy & Morphology
Muireann O'Reilly, Rachel Beatty, Shauna McBride, Benjamin Brennan, Peter Dockery, Garry P. Duffy
Summary: Chronic total occlusions (CTOs) occur in approximately 40% of individuals with symptomatic peripheral arterial disease and are indicative of critical limb ischaemia. Currently, few medical devices can effectively treat CTOs long-term, with amputation often required. This study aims to develop a workflow for further characterising the complex anatomy of CTOs and creating 3D models, which may be useful in producing a vascular CTO biomimetic for device testing. The study successfully establishes a workflow using high-resolution microcomputed tomography (mu CT) to generate 3D models of CTO components. This research holds great promise in improving device development for treating critical limb ischaemia.
JOURNAL OF ANATOMY
(2023)
Article
Cell Biology
Suzanna L. Prosser, Johnny Tkach, Ladan Gheiratmand, Jaeyoun Kim, Brian Raught, Ciaran G. Morrison, Laurence Pelletier
Summary: In this study, the researchers found that centriolar satellite and centrosomal proteins are crucial for the formation of aggresomes and the aggregation of disease-relevant proteins. They showed that satellites are required for the growth of aggresomal structure and this growth depends on the centrosomal proteins CP110, CEP97, and CEP290.
NATURE CELL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Olivier Mercey, Corinne Kostic, Eloise Bertiaux, Alexia G. Giroud, Yashar Sadian, David C. A. Gaboriau, Ciaran Morrison, Ning Chang, Yvan Arsenijevic, Paul Guichard, Virginie Hamel
Summary: Inherited retinal degeneration caused by the loss of photoreceptor cells is a major cause of human blindness. This study uses expansion microscopy and electron microscopy to uncover the molecular architecture of the connecting cilium (CC) and reveals that microtubules are connected by a CC inner scaffold containing POC5, CENTRIN, and FAM161A. The disruption of Fam161a leads to the loss of the CC inner scaffold, triggering microtubule doublet spreading and ultimately resulting in outer segment collapse and photoreceptor degeneration.
Article
Biochemistry & Molecular Biology
Marine H. Laporte, Imene B. Bouhlel, Eloiese Bertiaux, Ciaran G. Morrison, Alexia Giroud, Susanne Borgers, Juliette Azimzadeh, Michel Bornens, Paul Guichard, Anne Paoletti, Virginie Hamel
Summary: This study demonstrates the presence of a conserved SFI1/Centrin module that displays divergent functions in different organisms.
Article
Biochemistry & Molecular Biology
John J. Skoko, Juxiang Cao, David Gaboriau, Myriam Attar, Alparslan Asan, Lisa Hong, Candice E. Paulsen, Hongqiang Ma, Yang Liu, Hanzhi Wu, Trey Harkness, Cristina M. Furdui, Yefim Manevich, Ciaran G. Morrison, Erika T. Brown, Daniel Normolle, Maria Spies, Michael Ashley Spies, Kate Carroll, Carola A. Neumann
Summary: This study identifies RAD51 Cys319 as a functionally significant site for the redox regulation of homologous recombination (HR) and cellular responses to ionizing radiation (IR). The loss of peroxiredoxin 1 (PRDX1) inhibits RAD51 focus formation and HR DNA repair, leading to increased DNA damage and sensitization of cells to irradiation.
Article
Biotechnology & Applied Microbiology
Nupur Kohli, Konstantinos Theodoridis, Thomas A. G. Hall, Inigo Sanz-Pena, David C. A. Gaboriau, Richard J. van Arkel
Summary: This study aimed to evaluate a lab-based bioreactor model for assessing bone remodelling onto, into or around new implant technologies. The results showed that the samples cultured in the bioreactor exhibited greater tissue ongrowth, ingrowth and remodelling compared to those in static culture conditions. In addition, the mechanically tested samples from the bioreactor had approximately three times greater fixation strength.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Tianyi Yin, Lizhou Xu, Bruno Gil, Nabeel Merali, Maria S. S. Sokolikova, David C. A. Gaboriau, Daniel S. K. Liu, Ahmad Nizamuddin Muhammad Mustafa, Sarah Alodan, Michael Chen, Oihana Txoperena, Maria Arrastua, Juan Manuel Gomez, Nerea Ontoso, Marta Elicegui, Elias Torres, Danyang Li, Cecilia Mattevi, Adam E. E. Frampton, Long R. R. Jiao, Sami Ramadan, Norbert Klein
Summary: Biosensors based on graphene field effect transistors (GFETs) have the potential to develop portable diagnostic tools for early stage disease detection. By optimizing the analytical performance and test protocol, our GFET array platform can accurately detect pancreatic ductal adenocarcinoma (PDAC) in patients' plasma and differentiate different stages of cancer. The increased expression of GPC-1 cancerous exosomes leads to an improved signal response of GFET biosensors. This technology holds great promise for the rapid diagnosis of pancreatic cancer.
Article
Multidisciplinary Sciences
Richard J. Hewitt, Franz Puttur, David C. A. Gaboriau, Frederic Fercoq, Maryline Fresquet, William J. Traves, Laura L. Yates, Simone A. Walker, Philip L. Molyneaux, Samuel V. Kemp, Andrew G. Nicholson, Alexandra Rice, Edward Roberts, Rachel Lennon, Leo M. Carlin, Adam J. Byrne, Toby M. Maher, Clare M. Lloyd
Summary: This study reveals the impact of changes in extracellular matrix (ECM) composition secreted by lung fibroblasts on the migration and function of KRT5(+) cells in idiopathic pulmonary fibrosis (IPF), contributing to tissue remodeling in the fibrotic lung.
NATURE COMMUNICATIONS
(2023)
Article
Cell Biology
Francisco Goncalves-Santos, Ana R. G. De-Castro, Diogo R. M. Rodrigues, Maria J. G. De-Castro, Reto Gassmann, Carla M. C. Abreu, Tiago J. Dantas
Summary: This study investigates the impact of disabling the autoinhibition mechanism of dynein-2 on intraflagellar transport (IFT) using genome editing techniques in Caenorhabditis elegans. The results show that retrograde transport can be reactivated in IFT-A-deficient cilia by activating dynein-2 using a "hot-wiring" approach, providing functional evidence for dynein-2 autoinhibition during anterograde IFT and establishing key roles for IFT-A in regulating retrograde transport.
Article
Cell Biology
Ana R. G. De-Castro, Diogo R. M. Rodrigues, Maria J. G. De-Castro, Neide Vieira, Carmen Vieira, Ana X. Carvalho, Reto Gassmann, Carla M. C. Abreu, Tiago J. Dantas
Summary: The study identified WDR-60 as a key player in the recruitment and dynamics of dynein-2, with its loss leading to reduced and slower retrograde IFT trains. Disrupting the NPHP module at the transition zone almost fully restored ciliary exit of underpowered retrograde trains in wdr-60 mutants.
JOURNAL OF CELL BIOLOGY
(2022)
