A5068745105- DNA Repair Mechanisms
- CRISPR and Genetic Engineering
- Microtubule and mitosis dynamics
- RNA and protein synthesis mechanisms
- Epigenetics and DNA Methylation
- RNA modifications and cancer
- Cancer-related Molecular Pathways
- RNA regulation and disease
- Ubiquitin and proteasome pathways
- Telomeres, Telomerase, and Senescence
- Mitochondrial Function and Pathology
- Genomics and Chromatin Dynamics
- Pluripotent Stem Cells Research
- interferon and immune responses
- Plant Genetic and Mutation Studies
- Educational Assessment and Pedagogy
- Cell Image Analysis Techniques
- Bioinformatics and Genomic Networks
- Biotin and Related Studies
- Cancer, Hypoxia, and Metabolism
- Single-cell and spatial transcriptomics
- Protein Degradation and Inhibitors
- Heat shock proteins research
- PARP inhibition in cancer therapy
- Intelligent Tutoring Systems and Adaptive Learning
Science for Life Laboratory
2018-2025
Karolinska Institutet
2018-2025
ETH Zurich
2016
University of Zurich
2013-2015
Genetic code expansion via stop codon suppression is a powerful technique for engineering proteins in mammalian cells with site-specifically encoded noncanonical amino acids (ncAAs). Current methods rely on very few available tRNA/aminoacyl-tRNA synthetase pairs orthogonal cells, the pyrrolysyl pair from Methanosarcina mazei (Mma PylRS/PylT) being most active and versatile to date. We found human gut archaeon Methanomethylophilus alvus Mx1201 (Mx1201 be cells. show that this PylRS enzyme can...
DNA double-strand breaks (DSBs) are repaired by two major pathways: homologous recombination (HR) and non-homologous end-joining (NHEJ). The choice between HR NHEJ is highly regulated during the cell cycle. DNA-end resection, an evolutionarily conserved process that generates long stretches of single-stranded DNA, plays a critical role in pathway choice, as it commits cells to HR, while, at same time, suppressing NHEJ. As erroneous DSB repair source genomic instability-driven tumorigenesis,...
The regulation of DNA double-strand break (DSB) repair by phosphorylation-dependent signaling pathways is crucial for the maintenance genome stability; however, remarkably little known about molecular mechanisms which phosphorylation controls DSB repair. Here, we show that PIN1, a phosphorylation-specific prolyl isomerase, interacts with key factors and affects relative contributions homologous recombination (HR) nonhomologous end-joining (NHEJ) to We find PIN1-deficient cells display...
Genetically encoded fluorescent tags for visualization of proteins in living cells add six to several hundred amino acids the protein interest. While suitable most proteins, common easily match and exceed size microproteins 60 or less. The added molecular weight structure such tag may thus significantly affect vivo biophysical biochemical properties microproteins. Here, we develop single-residue terminal labeling (STELLA) that introduce a single noncanonical acid either at N- C-terminus...
Abstract The human genome contains thousands of potentially coding short open reading frames (sORFs). A growing set microproteins translated from these sORFs are known to have important cellular functions. However, the majority remains uncharacterised. Thus, larger screens find functional become more vital. Here, we performed a high-throughput CRISPR/Cas9 knock-out screen with customised library 11,776 sORFs, curated literature and databases identify essential for cancer cell line growth....
Cells recovering from the G2/M DNA damage checkpoint rely more on Aurora A-PLK1 signaling than cells progressing through an unperturbed G2 phase, but reason for this discrepancy is not known. Here, we devised a method based FRET reporter PLK1 activity to sort in distinct populations within phase. We employed mass spectroscopy characterize changes protein levels phase and validated that ATAD2 decrease proteasome-dependent manner. Comparing with damage, note at similar activities, contain...
Abstract Microproteins encoded by short open reading frames (sORFs) of less than 100 codons have been predicted to constitute a substantial fraction the eukaryotic proteome. However, relevance and roles majority microproteins remain undefined because only small these intriguing cellular players in-depth characterized so far. Here we use pooled overexpression screens with library 11’338 sORFs overcome challenge elucidating which thousands putative translated are biologically functional. As...
ABSTRACT Genetic code expansion via stop codon suppression is a powerful technique for engineering proteins in mammalian cells with site-specifically encoded non-canonical amino acids (ncAAs). Current methods rely on very few available tRNA/aminoacyl-tRNA synthetase pairs orthogonal cells, the pyrrolysyl pair from Methanosarcina mazei ( Mma PylRS/PylT) being most active and versatile to date. We found previously uncharacterized human gut archaeon Methanomethylophilus alvus Mx1201 be cells....
DNA double-strand breaks (DSBs) are highly deleterious lesions and their misrepair can promote genomic instability, a hallmark of cancer. DNA-end resection is cell cycle-regulated mechanism that required for the faithful repair DSBs. We recently discovered anaphase-promoting complex/cyclosome-Cdh1 (APC/C(Cdh1)) ubiquitin ligase responsible timely degradation CtBP-interacting protein (CtIP), key factor, providing new layer regulation DSB in human cells.
Abstract Human cells have evolved elaborate mechanisms for responding to DNA damage maintain genome stability and prevent carcinogenesis. For instance, the cell cycle can be arrested at different stages allow time repair. The APC/C-Cdh1 ubiquitin ligase regulates mitotic exit but is also implicated in damage-induced G2 arrest. However, it unknown whether directly participates Here we show that depletion of Cdh1 untransformed RPE-1 or several cancer lines results increased levels genomic...
Alterations in both cell cycle regulation and cellular metabolism are associated with cancer transformation, enzymes active the committed phase could represent vulnerabilities of cells. Here, we map metabolic events G1 SG2M phases by combining sorting mass spectrometry-based isotope tracing, revealing hundreds cycle-associated metabolites. In particular, arginine uptake ornithine synthesis was during transformed but not normal An integrative data analysis implicated arginase 2 (ARG2) enzyme...