A5066730926- Genomics and Chromatin Dynamics
- DNA Repair Mechanisms
- DNA and Nucleic Acid Chemistry
- RNA Research and Splicing
- Microtubule and mitosis dynamics
- Cellular Mechanics and Interactions
- Ubiquitin and proteasome pathways
- Cardiomyopathy and Myosin Studies
- Fungal and yeast genetics research
- Chromosomal and Genetic Variations
- Genomic variations and chromosomal abnormalities
- 14-3-3 protein interactions
- Autophagy in Disease and Therapy
- Toxin Mechanisms and Immunotoxins
- RNA and protein synthesis mechanisms
- Glycosylation and Glycoproteins Research
- Bacterial Genetics and Biotechnology
- Mitochondrial Function and Pathology
- Proteoglycans and glycosaminoglycans research
- Molecular Biology Techniques and Applications
- Microbial Natural Products and Biosynthesis
- Developmental Biology and Gene Regulation
- Antimicrobial Peptides and Activities
- Genetics, Aging, and Longevity in Model Organisms
- Marine Biology and Environmental Chemistry
Karolinska Institutet
2013-2024
Integrated Cardio Metabolic Centre
2022-2023
Umeå University
2010-2014
Tokyo Institute of Technology
2007
Research Institute of Molecular Pathology
2001
Stockholm University
1993-1998
Princeton University
1998
Sister-chromatid cohesion, established during replication by the protein complex cohesin, is essential for both chromosome segregation and double-strand break (DSB) repair. Normally, cohesion formation strictly limited to S phase of cell cycle, but DSBs can trigger also after DNA has been completed. The function this damage-induced remains unknown. In investigation, we show that repair in postreplicative cells yeast. Furthermore, it genome-wide induction a single DSB, controlled damage...
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...
Genome function depends on regulated chromosome folding, and loop extrusion by the protein complex cohesin is essential for this multilayered organization. The chromosomal positioning of controlled transcription, also localizes to stalled replication forks. However, role transcription in looping remains unclear. Here, we show that reduction chromosome-bound RNA polymerase weakens normal boundaries, allowing form new long-range cis interactions. Stress response genes induced inhibition are...
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...
The actin-binding protein, profilin, contains a src-homology (SH) 3-like fold (Schutt, C.E. et al., submitted), and its tight interaction with poly(L-proline) is reminiscent of the binding activity exhibited by SH3-domains. Here we demonstrate that replacements aromatic amino acids in hydrophobic patch on surface profilin molecule abolish poly(L-proline)-binding capacity. However, location this found another region than displaying structural similarities SH3 domains.
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...
Properties of human profilin I mutated in the major actin-binding site were studied and compared with wild-type using β/γ-actin as interaction partner. The mutants ranged affinity, from those that only weakly affected polymerization actin to one bound more strongly than profilin. With profilins, whose sequestering activity was low, concentration free monomers observed at steady-state [Afree], close seen alone ([Acc], critical polymerization). Profilin binding an intermediate affinity like...
Antibacterial peptides of the innate immune system combat pathogenic microbes, but often have additional roles in promoting inflammation and as growth factors during tissue repair. Midkine (MK) pleiotrophin (PTN) are only two members a family heparin-binding factors. They show restricted expression embryogenesis up-regulated neoplasia. In addition, MK shows constitutive inflammation-dependent some non-transformed tissues adult. present study, we that both PTN display strong antibacterial...
Abstract Pseudomonas are a common cause of hospital-acquired infections that may be lethal. ADP-ribosyltransferase activities exotoxin-S and -T depend on 14-3-3 proteins inside the host cell. By binding in phosphopeptide groove, an amphipathic C-terminal helix ExoS ExoT has been thought to crucial for their activation. However, crystal structures 14-3-3β:ExoS -ExoT complexes presented here reveal extensive hydrophobic interface is sufficient complex formation toxin We show C-terminally...
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...
We have obtained 15 HIV-2 isolates from the peripheral blood mononuclear cells (PBMCs) of 24 HIV-2-infected west African people. The frequency virus isolation correlated with severity infection; only three were 11 asymptomatic individuals, whereas was isolated nearly all (12 13) individuals symptoms. showed distinct replicative and cytopathic characteristics and, similarly to HIV-1 isolates, could be divided into two major groups: rapid/high slow/low. Rapid/high i.e. ability replicate in...
The DNA damage response triggered by bacterial cytolethal distending toxins (CDTs) is associated with activation of the actin-regulating protein RhoA and phosphorylation downstream-regulated mitogen-activated kinase (MAPK) p38, which promotes survival intoxicated (i.e. cells exposed to a toxin) cells. To identify effectors this CDT-induced response, we screened library 4492 Saccharomyces cerevisiae mutants that carry deletions in nonessential genes for reduced growth following inducible...