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| http://dx.doi.org/10.1371/journal.ppat.1011180 | DOI Listing |
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Adding a twist to the loops: the role of DNA superhelicity in the organization of chromosomes by SMC protein complexes.
Biochem Soc Trans
December 2024
Chair of Biochemistry and Cell Biology, Biocenter, Julius-Maximilians-Universität of Würzburg, Wurzburg, Germany.
Structural maintenance of chromosomes (SMC) protein complexes, including cohesin, condensin, and the Smc5/6 complex, are integral to various processes in chromosome biology. Despite their distinct roles, these complexes share two key properties: the ability to extrude DNA into large loop structures and the capacity to alter the superhelicity of the DNA double helix. In this review, we explore the influence of eukaryotic SMC complexes on DNA topology, debate its potential physiological function, and discuss new structural insights that may explain how these complexes mediate changes in DNA topology.
View Article and Find Full Text PDFNew thiourea derivatives that target the episomal silencing SMC5 protein to inhibit HBx-dependent viral DNA replication and gene transcription.
Virusdisease
December 2024
Department of Molecular and Cellular Medicine, Institute of Liver and Biliary Sciences, D-1, Vasant Kunj, New Delhi, 110 070 India.
Unlabelled: Antivirals such as nucleotide analogs (NAs) are potent inhibitors of hepatitis B virus (HBV) replication. However, NAs fail to diminish the signaling and mitogenic activities of the transactivator HBx protein. Earlier we have shown that thiourea derivative IR-415 (DSA-00) targeted HBx to down-regulate its target viral and host genes.
View Article and Find Full Text PDFAll eukaryotic SMC proteins induce a twist of -0.6 at each DNA loop extrusion step.
Sci Adv
December 2024
Department of Bionanoscience, Kavli Institute of Nanoscience Delft, Delft University of Technology, Delft, 2629HZ, Netherlands.
Eukaryotes carry three types of structural maintenance of chromosome (SMC) protein complexes, condensin, cohesin, and SMC5/6, which are ATP-dependent motor proteins that remodel the genome via DNA loop extrusion (LE). SMCs modulate DNA supercoiling but remains incompletely understood how this is achieved. Using a single-molecule magnetic tweezers assay that directly measures how much twist is induced by individual SMCs in each LE step, we demonstrate that all three SMC complexes induce the same large negative twist (i.
View Article and Find Full Text PDFSMC5/6-Mediated Transcriptional Regulation of Hepatitis B Virus and Its Therapeutic Potential.
Viruses
October 2024
I. Department of Internal Medicine, Center for Internal Medicine, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg, Germany.
Cells have developed various mechanisms to counteract viral infections. In an evolutionary arms race, cells mobilize cellular restriction factors to fight off viruses, targeted by viral factors to facilitate their own replication. The hepatitis B virus (HBV) is a small dsDNA virus that causes acute and chronic infections of the liver.
View Article and Find Full Text PDFLoop Extrusion Machinery Impairments in Models and Disease.
Cells
November 2024
Institute of Cytology and Genetics, 630090 Novosibirsk, Russia.
Structural maintenance of chromosomes (SMC) complexes play a crucial role in organizing the three-dimensional structure of chromatin, facilitating key processes such as gene regulation, DNA repair, and chromosome segregation. This review explores the molecular mechanisms and biological significance of SMC-mediated loop extrusion complexes, including cohesin, condensins, and SMC5/6, focusing on their structure, their dynamic function during the cell cycle, and their impact on chromatin architecture. We discuss the implications of impairments in loop extrusion machinery as observed in experimental models and human diseases.
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