A5049869893- CRISPR and Genetic Engineering
- Blood disorders and treatments
- DNA Repair Mechanisms
- Retinal Development and Disorders
- Cellular transport and secretion
- Acute Myeloid Leukemia Research
- PARP inhibition in cancer therapy
- RNA Research and Splicing
- interferon and immune responses
- Biotin and Related Studies
- Erythrocyte Function and Pathophysiology
- RNA modifications and cancer
- Protein Degradation and Inhibitors
- Axon Guidance and Neuronal Signaling
- Phagocytosis and Immune Regulation
- Ubiquitin and proteasome pathways
- Immune Cell Function and Interaction
- RNA regulation and disease
- T-cell and B-cell Immunology
- Peptidase Inhibition and Analysis
- Transgenic Plants and Applications
- Fungal Biology and Applications
- Cancer, Hypoxia, and Metabolism
- RNA and protein synthesis mechanisms
- Vitamin D Research Studies
ETH Zurich
2021-2024
Montreal Clinical Research Institute
2014-2022
McGill University
2018-2022
Institute for Biomedical Engineering
2021
Article28 August 2018Open Access Transparent process SHLD2/FAM35A co-operates with REV7 to coordinate DNA double-strand break repair pathway choice Steven Findlay Lady Davis Institute for Medical Research, Segal Cancer Centre, Jewish General Hospital, Montreal, QC, Canada Division of Experimental Medicine, McGill University, Search more papers by this author John Heath Vincent M Luo Department Microbiology and Immunology, Abba Malina orcid.org/0000-0002-8511-9005 Gerald Bronfman Oncology,...
Abstract Aberrant expression of receptor tyrosine kinase AXL is linked to metastasis. can be activated by its ligand GAS6 or other kinases, but the signaling pathways conferring metastatic activity are unknown. Here, we define AXL-regulated phosphoproteome in breast cancer cells. We reveal that stimulates phosphorylation a network focal adhesion (FA) proteins, culminating faster FA disassembly. Mechanistically, phosphorylates NEDD9, leading binding CRKII which turn associates with and...
Abstract Activation-induced deaminase (AID) mutates the immunoglobulin ( Ig ) genes to initiate somatic hypermutation (SHM) and class switch recombination (CSR) in B cells, thus underpinning antibody responses. AID a few hundred other loci, but most AID-occupied are spared. The mechanisms underlying productive deamination versus non-productive targeting unclear. Here we show that three clustered arginine residues define functional domain required for SHM, CSR, off-target activity cells...
Abstract Gfi1b is a transcriptional repressor expressed in hematopoietic stem cells (HSCs) and megakaryocytes (MKs). deficiency leads to expansion of both cell types abrogates the ability MKs respond integrin. Here we show that forms complexes with β-catenin, its co-factors Pontin52, CHD8, TLE3 CtBP1 regulates Wnt/β-catenin-dependent gene expression. In reporter assays, can activate TCF-dependent transcription Wnt3a treatment enhances this activation. This requires interaction between LSD1...
Throughout life, the tight equilibrium between cell death and prompt clearance of dead corpses is required to maintain a proper tissue homeostasis prevent inflammation. Following lactation, mammary gland involution triggered results in excessive epithelial cells that are rapidly cleared by phagocytes ensure returns its prepregnant state. Orthologs Dock1 (dedicator cytokinesis 1), Elmo Rac1 (ras-related C3 botulinum toxin substrate 1) Caenorhabditis elegans part signaling module linking...
Abstract The signalling output of many transmembrane receptors that mediate cell-cell communication is restricted by the endosomal sorting complex required for transport (ESCRT), but impact this machinery on Eph tyrosine kinase receptor function unknown. We identified ESCRT-associated adaptor protein HD-PTP as part an EphB2 proximity-dependent biotin identification (BioID) interactome, and confirmed association using co-immunoprecipitation. loss attenuates ephrin-B2:EphB2 signalling-induced...
The human CTLH/GID (hGID) complex emerged as an important E3 ligase regulating multiple cellular processes, including cell cycle progression and metabolism. However, the range of biological functions controlled by hGID remains unexplored. Here, we used proximity-dependent biotinylation (BioID2) to identify proteins interacting with complex, among them, substrate candidates that bind GID4 in a pocket-dependent manner. Biochemical assays revealed binds ubiquitinates ARHGAP11A, thereby...
Abstract Growth factor indepdendent 1 (GFI1) is a SNAG-domain, DNA binding transcriptional repressor which controls myeloid differentiation through molecular mechanisms and co-factors that still remain to be clearly identified. Here we show GFI1 associates with the chromodomain helicase protein 4 (CHD4) other components of Nucleosome remodeling deacetylase (NuRD) complex. In granulo-monocytic precursors, GFI1, CHD4 or GFI1/CHD4 complexes occupy sites enriched for histone marks associated...
Proximity-dependent biotinylation (BioID) screens are excellent tools to capture in cellulo interactomes for a large variety of baits, including transient and weak affinity interactions, as well localization-specific proximity components, which much harder detect with conventional approaches. Here, we describe the major starting steps detailed protocol on how perform BioID mammalian cells. We also mass spectrometry procedure bioinformatics pipeline data analysis. For complete details use...
Abstract The human CTLH/GID (hGID) complex emerged as an important E3 ligase regulating multiple cellular processes, including cell cycle progression and metabolic activity. However, the range of biological functions controlled by hGID remains unexplored. Here, we show that substrate receptor GID4 regulates growth migration. Biochemical assays combined with proximity-dependent biotinylation (BioID2) revealed E3-ligase targets Rho-GAP ARHGAP11A for degradation. Depletion or impeding binding...
SUMMARY DNA double-strand breaks (DSBs) can be repaired by two major pathways: non-homologous end-joining (NHEJ) and homologous recombination (HR). repair pathway choice is governed the opposing activities of 53BP1, in complex with its effectors RIF1 REV7, BRCA1. However, it remains unknown how 53BP1/RIF1/REV7 stimulates NHEJ restricts HR to S/G2 phases cell cycle. Using a mass spectrometry (MS)-based approach, we identify 11 high-confidence REV7 interactors elucidate role previously...
Homologous recombination (HR) plays an essential role in the maintenance of genome stability by promoting repair cytotoxic DNA double strand breaks (DSBs). More recently, HR pathway has emerged as a core component response to replication stress, part protecting stalled forks from nucleolytic degradation. In that regard, mammalian RAD51 paralogs (RAD51B, RAD51C, RAD51D, XRCC2, and XRCC3) have been involved both HR-mediated collapsed fork resolution. Still, it remains largely obscure how they...
Abstract Activation induced deaminase (AID) initiates class switch recombination (CSR) and somatic hypermutation of the antibody genes but also mutates “off-target” genes, with oncogenic consequences. Understanding mechanisms that render such loci susceptible to AID is therefore necessary. We identify H3K79 histone methyltransferase DOT1L as a nuclear AID-proximal factor required for CSR off-target activity, including IgH-cMyc translocations. Mechanistically, limits promoter-proximal...
Abstract The signalling output of many transmembrane receptors that mediate cell-cell communication is restricted by the endosomal sorting complex required for transport (ESCRT), but impact this machinery on Eph tyrosine kinase receptor function unknown. We identified ESCRT-associated adaptor protein HD-PTP as part an EphB2 BioID interactome, and confirmed association using co-immunoprecipitation. Although loss does not change expression, it attenuates ephrin-B2:EphB2 signalling-induced...
ABSTRACT The heterochromatin protein HP1 plays a central role in the maintenance of genome stability, particular by promoting homologous recombination (HR)-mediated DNA repair. However, little is still known about how controlled during this process. Here, we describe novel function POGO transposable element derived with ZNF domain (POGZ) regulation damage response vitro . POGZ depletion delays resolution double-strand breaks (DSBs) and correlates an increased sensitivity to different...
ABSTRACT GFI1 is a SNAG-domain, DNA binding transcriptional repressor which controls myeloid differentiation, in particular the formation of neutrophils. Here we show that interacts with chromodomain helicase CHD4 and other components “Nucleosome remodeling deacetylase” (NuRD) complex. In granulo-monocytic precursors, GFI1, or GFI1/CHD4 complexes occupy sites open chromatin enriched for histone marks associated active transcription suggesting recruits NuRD complex to target genes are...
Abstract GFI1 is a SNAG-domain, DNA binding transcriptional repressor which controls myeloid differentiation, in particular the formation of neutrophils. Here we show that interacts with chromodomain helicase CHD4 and other components “Nucleosome remodeling deacetylase” (NuRD) complex. In granulo-monocytic precursors, GFI1, or GFI1/CHD4 complexes occupy sites open chromatin enriched for histone marks associated active transcription suggesting recruits NuRD complex to target genes are...