A5087473783- DNA Repair Mechanisms
- Genomics and Chromatin Dynamics
- DNA and Nucleic Acid Chemistry
- Carcinogens and Genotoxicity Assessment
- Toxic Organic Pollutants Impact
- Genomic variations and chromosomal abnormalities
- Microtubule and mitosis dynamics
- RNA Research and Splicing
- Cancer therapeutics and mechanisms
- Ubiquitin and proteasome pathways
- Enterobacteriaceae and Cronobacter Research
- Circadian rhythm and melatonin
- Fungal and yeast genetics research
- Genetics, Aging, and Longevity in Model Organisms
- Bacteriophages and microbial interactions
- Chemical Analysis and Environmental Impact
- FOXO transcription factor regulation
- Air Quality and Health Impacts
- Chromosomal and Genetic Variations
Karolinska Institutet
2011-2024
Integrated Cardio Metabolic Centre
2022-2023
Osaka Prefecture University
2004-2013
Structural maintenance of chromosomes (SMC) protein complexes are essential for the spatial organization chromosomes1. Whereas cohesin and condensin organize by extrusion DNA loops, molecular functions third eukaryotic SMC complex, Smc5/6, remain largely unknown2. Using single-molecule imaging, we show that Smc5/6 forms loops extrusion. Upon ATP hydrolysis, reels symmetrically into at a force-dependent rate one kilobase pair per second. extrudes in form dimers, whereas monomeric...
The structural maintenance of chromosomes (SMC) protein complexes—cohesin, condensin, and the Smc5/6 complex (Smc5/6)—are essential for chromosome function. At molecular level, these complexes fold DNA by loop extrusion. Accordingly, cohesin creates loops in interphase, condensin compacts mitotic chromosomes. However, role Smc5/6's recently discovered extrusion activity is unknown. Here, we uncover that associates with transcription-induced positively supercoiled at cohesin-dependent...
The structural maintenance of chromosome (SMC) protein complexes cohesin and condensin the Smc5/6 complex (Smc5/6) are crucial for dynamics stability. All contain essential ATPase domains, interact with chromosomes through topological entrapment DNA. However, how binds DNA has remained largely unknown. Here, we show that purified a mechanism requires ATP hydrolysis by circular to be established. This also promotes topoisomerase 2-dependent catenation plasmids, suggesting interconnects two...
The cohesin complex, which is essential for sister chromatid cohesion and chromosome segregation, also inhibits resolution of intertwinings (SCIs) by the topoisomerase Top2. cohesin-related Smc5/6 complex (Smc5/6) instead accumulates on chromosomes after Top2 inactivation, known to lead a buildup unresolved SCIs. This suggests that can influence chromosomal association via its role in SCI protection. Using high-resolution ChIP-sequencing, we show localization budding yeast duplicated indeed...
Abstract In C. elegans, the conserved transcription factor DAF-16/FOXO is a powerful aging regulator, relaying dire conditions into expression of stress resistance and longevity promoting genes. For some these functions, including low insulin/IGF signaling (IIS), DAF-16 depends on protein SMK-1/SMEK, but how SMK-1 exerts this role has remained unknown. We show that functions as part specific Protein Phosphatase 4 complex (PP4 ). Loss PP4 hinders transcriptional initiation at several...
Abstract 3‐Nitrobenzanthrone (3‐NBA) is a potent mutagen and potential human carcinogen identified in diesel exhaust ambient air particulate matter. Previously, we detected the formation of 3‐NBA‐derived DNA adducts rodent tissues by 32 P‐postlabeling, all which are derived from reductive metabolites 3‐NBA bound to purine bases, but structural identification these has not yet been reported. We have now prepared adduct standards for P‐postlabeling reacting N ‐acetoxy‐3‐aminobenzanthrone (...
Meiosis is a specialized cell division used by diploid organisms to form haploid gametes for sexual reproduction. Central this reductive repair of endogenous DNA double-strand breaks (DSBs) induced the meiosis-specific enzyme Spo11. These DSBs are repaired in process called homologous recombination using sister chromatid or chromosome as template, with homolog being preferred substrate during meiosis. Specific products inter-homolog recombination, crossovers, essential proper segregation at...
Abstract Structural Maintenance of Chromosomes (SMC) protein complexes are essential for the spatial organization chromosomes. While cohesin and condensin organize chromosomes by extruding DNA loops, molecular functions third eukaryotic SMC complex, Smc5/6, remain largely unknown. Using single-molecule imaging, we reveal that Smc5/6 forms loops extrusion. Upon ATP-hydrolysis, symmetrically reels into at a force-dependent rate 1 kilobase pairs per second. extrudes in form dimer, while...
Structural maintenance of chromosome (SMC) complexes organize and regulate genomes via DNA loop extrusion. During this process, the increase size by reeling in from one or both sides loop. The factors governing symmetry remain unclear. Here, we combine single-molecule analysis molecular dynamic simulations to investigate extrusion various SMC complexes. We find that whereas monomeric condensin cohesin are one-sided extruders, dimeric SMCs, such as Smc5/6 Wadjet, is tension dependent. At low...
SUMMARY The Structural Maintenance of Chromosome (SMC) protein complexes cohesin, condensin and the Smc5/6 complex (Smc5/6) are essential for chromosome function. At molecular level, these fold DNA by loop extrusion. Accordingly, cohesin creates loops in interphase, compacts mitotic chromosomes. However, role Smc5/6’s recently discovered extrusion activity is unknown. Here, we uncover that associates with transcription-induced positively supercoiled chromosomal at cohesin-dependent...
Particles present in urban air pollution are mainly derived from diesel- and gasoline-fueled vehicles. Exhaust emission is able to cause several health effects humans including mutagenicity carcinogenicity. Polycyclic aromatic hydrocarbons (PAHs) were measured diesel gasoline particulate extracts DNA binding CT (±S9 ±XO) was investigated. A large difference content of 14 PAHs observed, showing higher concentration PAHs, 6 carcinogenic benzo[a]pyrene (B[a]P) than extracts. Selected PAH...
Abstract Structural Maintenance of Chromosomes (SMC) protein complexes are essential for the spatial organization chromosomes. While cohesin and condensin organize chromosomes by extruding DNA loops, molecular functions third eukaryotic SMC complex, Smc5/6, remain largely unknown. Using single-molecule imaging, we reveal that Smc5/6 forms loops extrusion. Upon ATP-hydrolysis, symmetrically reels into at a force-dependent rate 1 kilobase pairs per second. extrudes in form dimer, while...