Article
Chemistry, Analytical
Lahari Uppuluri, Tanaya Jadhav, Yilin Wang, Ming Xiao
Summary: This study introduces a universal multicolor mapping strategy in nanochannels combining conventional sequence motif labeling with Cas9-mediated target-specific labeling, which enables accurate detection of structural variations and estimation of genomic repeat copy numbers. The method was validated for assessing biomarkers related to muscular dystrophy and aging-related diseases.
ANALYTICAL CHEMISTRY
(2021)
Review
Biophysics
Karolin Frykholm, Vilhelm Muller, K. K. Sriram, Kevin D. Dorfman, Fredrik Westerlund
Summary: Nanofluidic structures provide a powerful platform for detailed analysis of DNA. By confining DNA to nanochannels, it can be stretched to near its full length without any chemical modifications. The versatility of nanofabrication allows for the design of devices tailored for specific applications, such as controlling confinement or enabling exchange of reagents. The two important applications discussed in this review are optical DNA mapping and DNA-protein interactions, showcasing the power of DNA confinement and nanofluidics in genomics, molecular biology, and biophysics.
QUARTERLY REVIEWS OF BIOPHYSICS
(2022)
Article
Biochemistry & Molecular Biology
Clemence Claussin, Jacob Vazquez, Iestyn Whitehouse
Summary: This study developed a method called Replicon-seq, which can accurately define the movement of individual replisomes across the genome. Using this method, the study found that sister replisomes function autonomously and progress through chromatin with remarkable consistency. Replication forks pause briefly when encountering obstacles but quickly resume synthesis, and the helicase Rrm3 plays a critical role in mitigating the effect of protein barriers and facilitating efficient termination.
Article
Multidisciplinary Sciences
Dean Huang, Anna E. Johnson, Brandon S. Sim, Teresa W. Lo, Houra Merrikh, Paul A. Wiggins
Summary: Quantitative characterization of nucleic-acid-bound molecular motors' dynamics in living cells is crucial for understanding the mechanistic basis of the central dogma. Lag-time analysis was developed to measure in vivo dynamics, providing quantitative locus-specific measurements of fork velocity and replisome pause durations. The observed dynamics are both locus and time dependent, even in wild-type cells, showing locus-specific pauses and temporal fork velocity oscillations.
NATURE COMMUNICATIONS
(2023)
Article
Cell Biology
Shin-ichiro Takebayashi, Tyrone Ryba, Kelsey Wimbish, Takuya Hayakawa, Morito Sakaue, Kenji Kuriya, Saori Takahashi, Shin Ogata, Ichiro Hiratani, Katsuzumi Okumura, Masaki Okano, Masato Ogata
Summary: Multiple epigenetic pathways, including DNA methylation, influence DNA replication timing. Loss of Dnmts has complex and diverse effects on the mammalian DNA replication landscape, with subtle but reproducible changes observed in various genomic regions. Replication timing in pericentromeric heterochromatin is correlated with redistribution of H3K27me3 induced by DNA hypomethylation.
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
Biochemistry & Molecular Biology
Bryan J. Visser, Sonum Sharma, Po J. Chen, Anna B. McMullin, Maia L. Bates, David Bates
Summary: DNA supercoiling is a key regulator of DNA metabolic processes, but a reliable genomic assay for supercoiling is lacking. In this study, a high-resolution method (Psora-seq) is presented to measure whole-genome supercoiling, and it is applied in Escherichia coli to observe a supercoiling landscape that is well correlated to transcription. The results indicate that transcription is the major determinant of chromosome supercoiling, while DNA replication also strongly influences supercoiling.
NUCLEIC ACIDS RESEARCH
(2022)
Review
Biochemical Research Methods
Jonathan Jeffet, Sapir Margalit, Yael Michaeli, Yuval Ebenstein
Summary: The human genome contains multiple layers of information that go beyond the genetic sequence, leading to differences in phenotype even with identical genetics. Genetic and epigenetic patterns work together to maintain specific cell functions in health and disease. Single-molecule optical genome mapping allows for the study of genetic and epigenetic patterns on a single-molecule level, providing insights inaccessible by sequencing technologies.
BIOCHEMISTRY: ONE MOLECULE AT A TIME
(2021)
Article
Biochemistry & Molecular Biology
Yaqun Liu, Xia Wu, Yves d'Aubenton-Carafa, Claude Thermes, Chun-Long Chen
Summary: During cell division, the activation of thousands of DNA replication origins ensures the complete duplication of the human genome. However, replication fork progression can be hindered by transcription-replication conflicts, with head-on conflicts being more detrimental. In this study, a bioinformatics toolkit called OKseqHMM was developed to analyze Okazaki fragment sequencing data and accurately predict replication initiation and termination, as well as replication fork directionality, in various organisms. This toolkit can greatly contribute to studying genome instability and its impact on human health.
NUCLEIC ACIDS RESEARCH
(2023)
Review
Biochemistry & Molecular Biology
Hui Zhang
Summary: DNA replication licensing is tightly regulated in eukaryotic cells to ensure proper replication initiation and prevent re-replication, with key mechanisms involving degradation of Cdt1 protein by CRL4(Cdt2) ubiquitin E3 ligase. The interaction between Cdt1 and PCNA, facilitated by the PIP box domain, plays a crucial role in this process, highlighting the importance of regulating DNA replication and genome stability.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Physics, Fluids & Plasmas
Lili Zeng, Walter W. Reisner
Summary: In this study, molecular dynamics simulation was used to investigate the nonequilibrium physics of single nanochannel-confined semiflexible polymers in a homogeneous flow field. The results showed that the flow-based compression of the polymer against the end of the nanochannel led to a distinct organization of folds and circular coils. The organization varied with the stiffness of the chains and the flow speed, but was ultimately determined by the minimization of the total chain free energy.
Editorial Material
Biochemistry & Molecular Biology
Ilona Faustova, Mart Loog
Summary: Study by Hossain et al. (2021) reveals that ORC1 and CDC6 interact during pre-replicative complex formation in G1, mediated by SLiMs in IDRs and regulated by CDKs.
Article
Virology
Tareq Abualfaraj, Nafiseh Chalabi Hagkarim, Robert Hollingworth, Laura Grange, Satpal Jhujh, Grant S. Stewart, Roger J. Grand
Summary: The Ad12E1B55K protein affects cellular DNA damage response pathways and DNA replication by interacting with multiple proteins, leading to genomic instability.
Article
Biochemistry & Molecular Biology
Ziv Itzkovich, Karan Choudhary, Matan Arbel, Martin Kupiec
Summary: Timely and complete replication of the genome is crucial for life. The PCNA ring is essential for DNA replication and repair by enhancing the processivity of DNA polymerases and recruiting proteins involved in DNA replication-associated processes. The ELG1 gene encodes a protein that unloads PCNA from chromatin and its deletion results in genome instability, sensitivity to DNA damage, defects in genomic silencing, high mutation rates, and other significant phenotypes. This study demonstrates that the role of Elg1 in maintaining genome stability is primarily attributed to its effects on PCNA unloading, highlighting the importance of PCNA unloading for proper chromatin structure and genome stability.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biology
Marina Schrecker, Juan C. Castaneda, Sujan Devbhandari, Charanya Kumar, Dirk Remus, Richard K. Hite
Summary: The research discovered that PCNA can adopt both open and closed conformations in the RFC:PCNA:DNA complex, allowing for direct insertion of dsDNA. Additionally, the study revealed that the RFC-catalyzed loading of PCNA onto DNA involves multiple steps, with partial melting facilitating lateral insertion into the central RFC:PCNA channel.
Letter
Oncology
Jean-Sebastien Hoffmann
BULLETIN DU CANCER
(2021)
Article
Oncology
Melanie K. Prodhomme, Roxane M. Pommier, Camille Franchet, Frederique Fauvet, Valerie Bergoglio, Pierre Brousset, Anne-Pierre Morel, Anne-Cecile Brunac, Mojgan Devouassoux-Shisheboran, Virginie Petrilli, Caroline Moyret-Lalle, Jean-Sebastien Hoffmann, Alain Puisieux, Agnes Tissier
Summary: The study demonstrated that ZEB1 represses the expression of POLQ, inhibiting TMEJ activity and controlling genome integrity in breast cancer cells. This reveals an original mechanism of TMEJ regulation and highlights ZEB1 as a key player in maintaining genome stability during cancer progression.
Article
Biochemistry & Molecular Biology
Elisa Mentegari, Federica Bertoletti, Miroslava Kissova, Elisa Zucca, Silvia Galli, Giulia Tagliavini, Anna Garbelli, Antonio Maffia, Silvia Bione, Elena Ferrari, Fabrizio d'Adda di Fagagna, Sofia Francia, Simone Sabbioneda, Liuh-Yow Chen, Joachim Lingner, Valerie Bergoglio, Jean-Sebastien Hoffmann, Ulrich Hubscher, Emmanuele Crespan, Giovanni Maga
Summary: This study reveals that silencing human DNA polymerase (Pol lambda) in ALT cells represses ALT activity and induces telomeric stress, while replication stress in the absence of Pol lambda strongly affects the survival of ALT cells. Additionally, Pol lambda can promote annealing of telomeric repeats and is regulated by TERRA and replication protein A, with the POT1/TPP1 heterodimer stimulating Pol lambda activity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Domenico Maiorano, Jana El Etri, Camille Franchet, Jean-Sebastien Hoffmann
Summary: Genome instability plays a crucial role in tumor formation and treatment, but excessive instability may suppress tumorigenesis and be associated with a better prognosis. Specialized DNA polymerases play a key role in reducing extreme genetic instability, helping to avoid or repair DNA damage.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
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)
Article
Biology
Solenne Gaillard, Virginie Charasson, Cyril Ribeyre, Kader Salifou, Marie-Jeanne Pillaire, Jean-Sebastien Hoffmann, Angelos Constantinou, Didier Trouche, Marie Vandromme
Summary: KDM5A and KDM5B histone-demethylases play crucial roles in replication stress response and tolerance, positively regulating RRM2 and activated Chk1. They are major players in RS management, and drugs targeting their enzymatic activity may not fully address all cancer-related consequences of their overexpression.
Article
Biochemistry & Molecular Biology
Audrey Lejart, Siham Zentout, Catherine Chapuis, Ostiane D'Augustin, Rebecca Smith, Gilles Salbert, Sebastien Huet
Summary: The N-terminal domain of the TET1 protein plays a new role in regulating chromatin architecture. This domain promotes the formation of compact chromatin structure, leading to reduced exchange rate of core histones and partial dissociation of the histone linker. This chromatin reorganization process is independent of the CXXC domain and is associated with global shutdown of transcription and an increase in heterochromatin-associated histone epigenetic marks.
Article
Biochemical Research Methods
Inga Tijunelyte, Jeffrey Teillet, Paul Bruand, Remi Courson, Aurelie Lecestre, Pierre Joseph, Aurelien Bancaud
Summary: This study optimized a fluorimetry-based DNA detection technology by controlling the concentration of linear targets and probes. It was found that using specific lengths of target and probe, as well as chips fabricated with grayscale lithography, significantly enhanced sensitivity and detection range while maintaining a short detection time.
Article
Biochemistry & Molecular Biology
Rebecca Smith, Siham Zentout, Magdalena Rother, Nicolas Bigot, Catherine Chapuis, Alexandra Mihut, Florian Franz Zobel, Ivan Ahel, Haico van Attikum, Gyula Timinszky, Sebastien Huet
Summary: The study reveals that HPF1 is involved in early stages of DNA repair by regulating ADP-ribosylation signaling and damaged chromatin conformation.
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Ostiane D'Augustin, Virginie Gaudon, Capucine Siberchicot, Rebecca Smith, Catherine Chapuis, Jordane Depagne, Xavier Veaute, Didier Busso, Anne-Marie Di Guilmi, Bertrand Castaing, J. Pablo Radicella, Anna Campalans, Sebastien Huet
Summary: The DNA-glycosylase OGG1 constantly samples the DNA by rapidly alternating between diffusion within the nucleoplasm and short transits on the DNA, which is crucial for its recruitment to oxidative lesions. The sampling process is tightly regulated by the residue G245, while the residues Y203, N149, and N150 differentially regulate the sampling of the DNA and recruitment to oxidative lesions based on previous structural data.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Genetics & Heredity
Daniel de Barcellos Azambuja, Helena de Castro e Gloria, Gabriel e Silva Montenegro, Antonio Nocchi Kalil, Jean-Sebastien Hoffmann, Natalia Motta Leguisamo, Jenifer Saffi
Summary: Through evaluating the gene expression in tumor specimens and healthy tissues of 63 colorectal cancer (CRC) patients, it was found that the MRE11 homologous recombination repair gene is significantly overexpressed in CRC, particularly in primary tumors of higher stages, and mostly in right-side CRC, which has the worst prognosis. Furthermore, high MRE11 expression is associated with shorter overall survival and higher risk of death. Therefore, monitoring MRE11 expression could serve as both a predictor of outcome and a marker for selecting treatments for CRC patients.
Article
Biochemistry & Molecular Biology
Guillaume Labrousse, Pierre Vande Perre, Genis Parra, Marion Jaffrelot, Laura Leroy, Frederic Chibon, Frederic Escudie, Janick Selves, Jean-Sebastien Hoffmann, Rosine Guimbaud, Malik Lutzmann
Summary: The exonuclease domain of DNA polymerases epsilon's catalytic subunit (POLE) plays a role in proofreading by removing misincorporated nucleotides. Certain mutations in the POLE exonuclease domain, such as N363K, not only increase single nucleotide substitutions but also cause DNA damage and chromosome instability. This study highlights the importance of assessing both the mutational potential and genetic instability for the classification and treatment of POLE-mutated tumors.
Review
Materials Science, Biomaterials
Daniel Alcaide, Jean Cacheux, Aurelien Bancaud, Rieko Muramatsu, Yukiko T. Matsunaga
Summary: The debate over solute transport mechanisms in brain tissues, particularly regarding the blood-brain barrier and transport through the brain parenchyma, has medical relevance in understanding brain clearance. Experimental studies on living humans and animals have limitations, necessitating detailed microscopic observations, ex vivo tissue, simplified in vitro brain models, and computational models to understand brain transport mechanisms. Lack of standardization in these experimental approaches limits the generality of conclusions. This review highlights the output and limitations of modern brain solute transport studies, emphasizing the importance of in vitro and computational/mathematical models in understanding solute transport in brain tissue.
BIOMATERIALS SCIENCE
(2023)
Article
Oncology
Pascale Palassin, Marion Lapierre, Sandrine Bonnet, Marie-Jeanne Pillaire, Balazs Gyorffy, Catherine Teyssier, Stephan Jalaguier, Jean-Sebastien Hoffmann, Vincent Cavailles, Audrey Castet-Nicolas
Summary: This study reveals that RIP140 plays a role in maintaining microsatellite stability through positively regulating the expression of the POLK gene. The regulation of POLK gene expression by RIP140 involves the p53 tumor suppressor. The correlation between RIP140 and POLK gene expression was observed in CRC patient samples. Furthermore, it was found that cells lacking the Rip140 gene had an increased cellular response to methyl methane sulfonate.
CANCER DRUG RESISTANCE
(2022)
