Article
Biochemistry & Molecular Biology
Yongze Yu, Weiwei Xu, Canxin Wen, Simin Zhao, Guangyu Li, Ran Liu, Zi-Jiang Chen, Yingying Qin, Jinlong Ma, Yajuan Yang, Shidou Zhao
Summary: In this study, Ube2t knockout mice showed defects in the proliferation of primordial germ cells (PGCs), resulting in severe loss of germ cells after birth. Deletion of UBE2T exacerbated DNA damage and activated the p53 pathway. The study also revealed that UBE2T resolves transcription-replication conflicts, protects common fragile sites, and promotes mitotic DNA synthesis to maintain the genomic stability of PGCs. Overall, these findings provide new insights into the function and regulatory mechanisms of the Fanconi anemia pathway in ensuring the normal development of PGCs.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2023)
Article
Biochemical Research Methods
Zeeshan Abbas, Mobeen Ur Rehman, Hilal Tayara, Kil To Chong
Summary: In this article, a unique artificial intelligence-based technique called ORI-Explorer is developed to recognize origins of replication sites (ORIs) in four different eukaryotic species. ORI-Explorer combines multiple feature engineering techniques and utilizes the CatBoost Classifier. It outperforms existing predictors and provides key insights into model success through the SHapley Additive exPlanation method. ORI-Explorer aims to aid community-wide efforts in discovering potential ORIs and developing verifiable biological hypotheses.
Article
Microbiology
Jun Chen, Guanlie Li, Haiqing He, Xin Li, Wenjing Niu, Di Cao, Ao Shen
Summary: Controlled regulation of genomic DNA synthesis is vital for herpesviruses, including HCMV, and the UL44 processivity factor plays a key role in viral DNA replication. Interaction between UL44 and UBC9, a SUMO-conjugating enzyme, was confirmed, shedding light on the role of sumoylation in regulating UL44 functions and HCMV replication. Additionally, the identification of the major sumoylation site on UL44's carboxy-terminal provides new insights into how sumoylation can affect viral DNA synthesis and progeny production in HCMV-infected cells.
FRONTIERS IN MICROBIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Christelle de Renty, Kelvin W. Pond, Mary K. Yagle, Nathan A. Ellis
Summary: BLM sumoylation plays a role in both normal and replication-stressed conditions. The study showed that cells with SUMO-mutant BLM exhibited defects in DNA replication, such as reduced fork restart and increased fork collapse. The SUMO-mutant BLM protein was found to be less dynamic and had a higher immobile fraction at collapsed replication forks. These findings provide important insights into the relationship between BLM sumoylation and replication stress.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Article
Plant Sciences
Therese C. Rytz, Juanjuan Feng, Jessica A. S. Barros, Richard D. D. Vierstra
Summary: The reversible conjugation of SUMO to other proteins plays an important role in plant development and stress defense. SUMO can be further modified by SUMOylation and ubiquitylation, but the functions of these modifications are not well understood. By replacing the essential SUMO isoforms with a lysine-null variant, the researchers found that these secondary modifications are involved in stress defense, DNA repair, and hormone signaling. The study also generated a new tool for investigating SUMO in plants.
Article
Cell Biology
Sofia Lobato-Gil, Jan B. Heidelberger, Chantal Maghames, Aymeric Bailly, Lorene Brunello, Manuel S. Rodriguez, Petra Beli, Dimitris P. Xirodimas
Summary: The study highlights the significance of NEDD8 in controlling biological processes through specific enzymes. By identifying unique NEDDylation sites and distinct proteomes, the research underscores the diverse role of canonical and atypical NEDDylation. Furthermore, the formation of poly-NEDD8 and other chains suggests potential molecular signals in response to proteotoxic stress.
Article
Multidisciplinary Sciences
Dylan A. Reid, Patrick J. Reed, Johannes C. M. Schlachetzki, Ioana I. Nitulescu, Grace Chou, Enoch C. Tsui, Jeffrey R. Jones, Sahaana Chandran, Ake T. Lu, Claire A. McClain, Jean H. Ooi, Tzu-Wen Wang, Addison J. Lana, Sara B. Linker, Anthony S. Ricciardulli, Shong Lau, Simon T. Schafer, Steve Horvath, Jesse R. Dixon, Nasun Hah, Christopher K. Glass, Fred H. Gage
Summary: Neurons, as the longest-lived cells in our bodies, lack DNA replication and rely on a limited repertoire of DNA repair mechanisms to maintain genome fidelity. Research has found that DNA repair in neurons is enriched at well-defined hotspots, which are associated with evolutionarily conserved elements of the human genome. These findings provide insights into the protection of genome integrity in the aging and disease of the nervous system.
Article
Cell Biology
Michela Damizia, Ludovica Altieri, Vincenzo Costanzo, Patrizia Lavia
Summary: This study reveals that NuSAP1 interacts with RANBP2 and forms proximity ligation products with SUMO2/3 peptides at key mitotic sites. Additionally, two new regulatory sites for NuSAP1 functions are identified, implicating RANBP2 in control of NuSAP1 activity.
Article
Genetics & Heredity
Karol Kramarz, Dorota Dziadkowiec
Summary: This article summarizes the functions of multiple eukaryotic SWI2/SNF2 DNA translocases, especially the Rad5/16-like enzymes with translocase, ubiquitin ligase, and SUMOylation activities. These enzymes play important roles in replication stress response, particularly at centromeres and telomeres.
Review
Biochemistry & Molecular Biology
Yanduo Zhang, Kailong Hou, Jinkai Tong, Haonan Zhang, Mengjie Xiong, Jing Liu, Shuting Jia
Summary: This review provides a comprehensive overview of the current findings on the regulation of ALT by Shelterin components, aiming to enhance the understanding of altered functions of Shelterin components in ALT cells and to identify potential targets for the treatment of ALT tumor cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Jing Zhang, Doug W. Chan, Shiaw-Yih Lin
Summary: Proliferating cells depend on DNA replication for accurate genome duplication. Cancer cells, including breast cancer cells, experience increased replication stress (RS) due to uncontrolled oncogenic activation, loss of key tumor suppressors, and defects in DNA repair machinery. Targeting RS in breast cancer shows promising efficacy in preclinical and early clinical trials, but the challenge lies in balancing drug toxicity and clinical efficacy, as well as the need for biomarkers to guide patient selection.
Review
Biochemistry & Molecular Biology
Susan M. Gasser, Francoise Stutz
Summary: The covalent linkage of Ubiquitin and SUMO to lysine residues plays important roles in DNA repair pathway choice and transcription regulation. SUMOylation mainly affects cellular processes by relocalizing modified proteins, particularly in response to DNA damage.
Article
Biochemistry & Molecular Biology
Lilas Courtot, Elodie Bournique, Chrystelle Maric, Laure Guitton-Sert, Miguel Madrid-Mencia, Vera Pancaldi, Jean-Charles Cadoret, Jean-Sebastien Hoffmann, Valerie Bergoglio
Summary: This study reveals that low replication stress can lead to advanced DNA replication timing, which is cell-type specific and involves large heterochromatin domains. These advanced events can be inherited by the next generation of cells, leading to changes in chromatin accessibility, replication origin landscape, and gene expression.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Commodore St Germain, Hongchang Zhao, Jacqueline H. Barlow
Summary: Transcription-replication interactions are essential processes in life, but they also pose potential threats to genome integrity due to obstacles such as R-loops, DNA supercoiling, DNA secondary structure, and chromatin-binding proteins. It is critical to maintain high fidelity and processivity of transcription and replication in a complex chromatin environment to avoid these threats. Various safeguards have evolved to navigate transcription-replication interactions and maintain genome integrity in mammalian cells.
Editorial Material
Cell Biology
Jean-Sebastien Hoffmann
Summary: The major challenge in DNA replication is to ensure the transmission of intact genetic material to daughter cells. Despite extensive research on the cellular responses to replication problems and their source, the transmission of genome modifications and their heritability in mitosis has been less documented. Recent studies have shown that low replication stress can impact the next generation of cells, transmitting DNA damage and altering the replication timing program of chromosomal domains in daughter cells. This progression of replication issues into mitosis and daughter cells may provide advantages by alerting cells to risky loci and offering an adaptive mechanism to anticipate future problems, especially in the context of cancer cell resistance to therapy.
Article
Surgery
Regent Lee, Ismail Cassimjee, Honglei Huang, Pierfrancesco Lapolla, Elisha Ngetich, Anirudh Chandrashekar, Philip Charles, Benedikt Kessler, Roman Fischer, Ashok Handa
Summary: This study discovered novel biomarkers for predicting AAA growth using a mass spectrometry proteomics pipeline. These biomarkers, including Attractin, showed significant correlation with future AAA growth and could be used to predict the growth of AAA.
Article
Surgery
Rebecca H. Vaughan, Jean-Claude Kresse, Louise K. Farmer, Marie L. Thezenas, Benedikt M. Kessler, Jan H. N. Lindeman, Edward J. Sharples, Gavin Welsh, Rikke Norregaard, Rutger J. Ploeg, Maria Kaisar
Summary: The study reveals that cytoskeletal proteins in brain death donor kidneys are susceptible to proteolytic cleavage, which may cause posttransplant dysfunction. Specific proteolytic fragments were detected in brain death kidneys but not in other types of donor kidneys.
AMERICAN JOURNAL OF TRANSPLANTATION
(2022)
Article
Chemistry, Medicinal
Mark Berney, Manav T. Manoj, Ellen M. Fay, Joanna F. McGouran
Summary: Certain cancers upregulate DNA interstrand crosslink repair pathways, contributing to resistance to chemotherapy drugs and poor prognoses. Inhibiting enzymes involved in interstrand crosslink repair is a promising strategy for improving cancer treatment efficacy. This study aimed to develop more effective SNM1A inhibitors by exploiting interactions with the phosphate-binding pocket adjacent to the enzyme's active site. The incorporation of a 5'-phosphate dramatically increased the potency of the inhibitors.
Article
Engineering, Biomedical
Murat Serhatlioglu, Emil Alstrup Jensen, Maria Niora, Anne Todsen Hansen, Christian Friberg Nielsen, Michelle Maria Theresia Jansman, Leticia Hosta-Rigau, Morten Hanefeld Dziegiel, Kirstine Berg-Sorensen, Ian David Hickson, Anders Kristensen
Summary: A compact microfluidic flow cytometer with viscoelastic flow focusing and fiber optical interface is demonstrated. The device allows for easy operation and interchangeable capillaries to achieve single-train particle focusing for a wide range of particle sizes. The system is integrated with optical imaging and other optofluidic modalities and achieves a high throughput of 3500 events s(-1).
ADVANCED NANOBIOMED RESEARCH
(2023)
Article
Biochemical Research Methods
Tehmina Bharucha, Bevin Gangadharan, Abhinav Kumar, Ashleigh C. Myall, Nazli Ayhan, Boris Pastorino, Anisone Chanthongthip, Manivanh Vongsouvath, Mayfong Mayxay, Onanong Sengvilaipaseuth, Ooyanong Phonemixay, Sayaphet Rattanavong, Darragh P. O'Brien, Iolanda Vendrell, Roman Fischer, Benedikt Kessler, Lance Turtle, Xavier de Lamballerie, Audrey Dubot-Peres, Paul N. Newton, Nicole Zitzmann, SEAe Consortium
Summary: A diagnostic signature consisting of nine proteins for Japanese encephalitis was developed using liquid chromatography and tandem mass spectrometry techniques. The accuracy of the signature was tested and validated, showing 82% accuracy. Further research and validation can help refine the signature for rapid diagnosis of Japanese encephalitis.
JOURNAL OF PROTEOME RESEARCH
(2023)
Article
Multidisciplinary Sciences
Larissa Dietz, Cara J. Ellison, Carlos Riechmann, C. Keith Cassidy, F. Daniel Felfoldi, Adan Pinto-Fernandez, Benedikt M. Kessler, Paul R. Elliott
Summary: Certain members of the inhibitor of apoptosis (IAP) family, including BIRC6, regulate cell death by inhibiting caspases, while SMAC antagonizes IAPs and promotes cell death. BIRC6 directly inhibits caspase-3 and-7 and ubiquitinates caspase-3,-7, and-9, working with noncanonical E1, UBA6. SMAC suppresses both mechanisms by competitively displacing caspases.
Article
Cell Biology
Cyriel Sebastiaan Olie, Adan Pinto-Fernandez, Andreas Damianou, Iolanda Vendrell, Hailiang Mei, Bianca den Hamer, Erik van der Wal, Jessica C. de Greef, Vered Raz, Benedikt M. Kessler
Summary: The ubiquitin proteasomal system plays a critical role in muscle physiology, but the function of deubiquitinating enzymes (DUBs) in muscle cells remains poorly understood. Through a genetic screen, we discovered that the depletion of USP18, a DUB, affects muscle cell differentiation. USP18 regulates differentiation initiation and maintenance independently of ISG15 and the ISG response. Alterations in gene networks and protein expression profiles were observed in the absence of USP18, leading to disrupted calcium homeostasis and reduced contractile force.
CELL DEATH & DISEASE
(2023)
Article
Pharmacology & Pharmacy
L. Leonie van Leeuwen, Mitchel J. R. Ruigrok, Benedikt M. Kessler, Henri G. D. Leuvenink, Peter Olinga
Summary: This study demonstrates the value of machine perfusion for administering antifibrotic drugs such as galunisertib and proves the effectiveness of ex vivo administration.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Hannah C. Scott, Simeon D. Draganov, Zhanru Yu, Benedikt M. Kessler, Adan Pinto-Fernandez
Summary: Bioactive lipids play important roles in cellular signaling events and are associated with human diseases. A liquid chromatography-dynamic multiple reaction monitoring-targeted mass spectrometry (LC-dMRM-MS) approach has been optimized for the analysis of eicosanoids and fatty acids in biological samples. By studying a cellular model of chronic myeloid leukemia (CML), it was found that immunomodulation by type I interferon (IFN-I) caused changes in the levels of specific lipids, potentially indicating their relevance in cancer inflammation and CML.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Rahul Bhowmick, Ian D. Hickson, Ying Liu
Summary: Mitotic DNA synthesis (MiDAS) is an unusual form of DNA replication that occurs during mitosis, which not only relates to intrinsically unstable loci but also completes the duplication of any under-replicated genomic region. Recent data suggests that MiDAS is a DNA repair process potentially involving multiple pathways working in parallel or sequentially. Therefore, understanding the causes of replication stress, vulnerable regions in the genome, and strategies for completing DNA replication outside of S phase is important for further research on MiDAS.
Article
Biochemistry & Molecular Biology
Yehuda M. Danino, Lena Molitor, Tamar Rosenbaum-Cohen, Sebastian Kaiser, Yahel Cohen, Ziv Porat, Hagai Marmor-Kollet, Corine Katina, Alon Savidor, Ron Rotkopf, Eyal Ben-Isaac, Ofra Golani, Yishai Levin, David Monchaud, Ian D. Hickson, Eran Hornstein
Summary: This study reveals a novel role of Bloom's syndrome protein in the regulation of cytoplasmic processes. It demonstrates that BLM can unwind RNA G-quadruplexes and acts as a negative regulator of stress granule formation.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Cell Biology
Dedrick Kok Hong Chan, Amit Mandal, Svenja Hester, Zhanru Yu, Geoff Stuart Higgins, Benedikt Mathias Kessler, Roman Fischer, Simon James Alexander Buczacki
Summary: This study found that FBXW7 gene mutation in colorectal cancer cells leads to DNA damage in neighboring wildtype cells. The study also discovered that FBXW7 mutant cells induce DNA damage through the secretion of AKAP8 protein. These findings highlight the importance of understanding the local effects of cancer driver mutations between subclonal populations.
CELL DEATH DISCOVERY
(2023)
Article
Multidisciplinary Sciences
Dannielle Wellington, Zixi Yin, Zhanru Yu, Raphael Heilig, Simon Davis, Roman Fischer, Suet Ling Felce, Elie Antoun, Philip Hublitz, Ryan Beveridge, Danning Dong, Guihai Liu, Xuan Yao, Yanchun Peng, Benedikt M. Kessler, Tao Dong
Summary: This study reveals that mutations in flanking regions of SARS-CoV-2 epitopes can affect proteasomal processing and T cell activation, leading to immune escape or enhancement. These findings have important implications for the design of COVID-19 vaccines.
Article
Biochemistry & Molecular Biology
Elizabeth R. Dellar, Iolanda Vendrell, Kevin Talbot, Benedikt M. Kessler, Roman Fischer, Martin R. Turner, Alexander G. Thompson
Summary: This study used mass spectrometry with library-free data-independent acquisition to analyze the CSF proteome of ALS patients. It identified proteins correlated with clinical variables and strengthened the candidacy of CHIT1 and UCHL1 as biomarkers for ALS. The study also highlighted inflammatory and endoplasmic reticulum proteins as potential prognostic biomarkers.
JOURNAL OF NEUROCHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Leonie van Leeuwen, Leonie H. Venema, Raphael Heilig, Henri G. D. Leuvenink, Benedikt M. Kessler
Summary: This study investigated the effects of doxycycline on protein degradation and the urinary proteome during hypothermic machine perfusion (HMP). The results showed that doxycycline altered protein degradation during HMP, indicating its protective effects. The study also revealed metabolic and complement coagulation pathway alterations during machine perfusion, which could be targeted to attenuate ischemia-reperfusion injury (IRI).
CURRENT ISSUES IN MOLECULAR BIOLOGY
(2022)