A5063817650- Microtubule and mitosis dynamics
- Ubiquitin and proteasome pathways
- Epigenetics and DNA Methylation
- Cellular transport and secretion
- Genomics and Chromatin Dynamics
- DNA Repair Mechanisms
- interferon and immune responses
- RNA modifications and cancer
- Bacterial Genetics and Biotechnology
- Monoclonal and Polyclonal Antibodies Research
- Advanced Proteomics Techniques and Applications
- Cellular Mechanics and Interactions
- Chromosomal and Genetic Variations
- RNA and protein synthesis mechanisms
- Genetics and Neurodevelopmental Disorders
University of Copenhagen
2010-2019
Novo Nordisk Foundation
2013-2019
Business Innovation Centre
2011
Activation of oncogenes or inhibition WEE1 kinase deregulates cyclin-dependent (CDK) activity and leads to replication stress; however, the underlying mechanism is not understood. We now show that elevation CDK by rapidly increases initiation replication. This nucleotide shortage reduces fork speed, which followed SLX4/MUS81-mediated DNA double-strand breakage. Fork speed normalized break (DSB) formation suppressed when CDT1, a key factor for initiation, depleted. Furthermore, addition...
BubR1 is a central component of the spindle assembly checkpoint that inhibits progression into anaphase in response to improper kinetochore-microtubule interactions. In addition, also helps stabilize interactions by counteracting Aurora B kinase but mechanism behind this not clear. Here we show directly binds B56 family protein phosphatase 2A (PP2A) regulatory subunits through conserved motif phosphorylated cyclin-dependent 1 (Cdk1) and polo-like (Plk1). Two highly hydrophobic residues...
Maintenance of genome integrity is critical importance to cells. To identify key regulators genomic integrity, we screened a human cell line with kinome small interfering RNA library. WEE1, major regulator mitotic entry, and CHK1 were among the genes identified. Both kinases are important negative CDK1 -2. Strikingly, WEE1 depletion rapidly induced DNA damage in S phase newly replicated DNA, which was accompanied by marked increase single-stranded DNA. This dependent on -2 as well...
The eukaryotic cell cycle is regulated by multiple ubiquitin-mediated events, such as the timely destruction of cyclins and replication licensing factors. histone H4 methyltransferase SET8 (Pr-Set7) required for chromosome compaction in mitosis maintenance genome integrity. In this study, we show that targeted degradation during S phase CRL4(CDT2) ubiquitin ligase a proliferating nuclear antigen (PCNA)–dependent manner. requires conserved degron responsible its interaction with PCNA...
Highlights•APC/C activity is powered by three E2 enzymes, UBE2S, UBE2C, and UBE2D•UBE2S-catalyzed ubiquitylation has an important function in cells lacking UBE2C•Reduction APC/C renders the SAC unessential human cells•UBE2C-UBE2S deletion provides synthetic viability to MAD2 deletionSummaryThe anaphase-promoting complex/cyclosome (APC/C) spindle assembly checkpoint (SAC), which inhibits APC/C, are essential determinants of mitotic timing faithful division genetic material. Activation known...
The spindle assembly checkpoint (SAC) ensures accurate chromosome segregation during mitosis by delaying the activation of anaphase-promoting complex/cyclosome (APC/C) in response to unattached kinetochores. Mad2 protein is essential for a functional because it binds directly Cdc20, mitotic co-activator APC/C, thereby inhibiting progression into anaphase. exists at least 2 different conformations, open-Mad2 (O-Mad2) and closed-Mad2 (C-Mad2), with latter representing active form that able...
Background Global residue-specific amino acid mutagenesis can provide important biological insight and generate proteins with altered properties, but at the risk of protein misfolding. Further, targeted libraries are usually restricted to a handful acids because there is an exponential correlation between number residues randomized size resulting ensemble. Using GFP as model protein, we present strategy, termed evolution via codon elimination, through which simplified, native-like...
ABSTRACT The spindle assembly checkpoint (SAC) inhibits the anaphase-promoting complex/cyclosome (APC/C) in response to unattached kinetochores by generating a diffusible inhibitor termed mitotic complex (MCC). At metaphase, rapid activation of APC/C requires removal MCC, process that has been shown depend on E2 enzymes, UBE2C and UBE2S. Here we investigate vivo role enzymes SAC silencing using CRISPR/Cas9 genetically engineered HCT116 or UBE2S null cell lines. Using live assays, show make...