A5079388456- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- HIV Research and Treatment
- CRISPR and Genetic Engineering
- Cytomegalovirus and herpesvirus research
- Multiple Myeloma Research and Treatments
- DNA Repair Mechanisms
- Monoclonal and Polyclonal Antibodies Research
- Immunotherapy and Immune Responses
- Chronic Lymphocytic Leukemia Research
- Immunodeficiency and Autoimmune Disorders
- Transgenic Plants and Applications
- Cancer Genomics and Diagnostics
- Epigenetics and DNA Methylation
- Aquaculture disease management and microbiota
- Biochemical and Molecular Research
- Cancer Immunotherapy and Biomarkers
- vaccines and immunoinformatics approaches
- Plant Virus Research Studies
- Advanced biosensing and bioanalysis techniques
- Bacillus and Francisella bacterial research
- HIV-related health complications and treatments
- Bacteriophages and microbial interactions
- RNA and protein synthesis mechanisms
- Diabetes and associated disorders
Simon Fraser University
2019-2025
Memorial University of Newfoundland
2014-2025
Ohio Attorney General's Office
2017
St. John's University
2012
University of Toronto
1998-2011
York University
2005
Keele University
2005
Massachusetts General Hospital
2003
Harvard University
2003
Ontario Institute for Cancer Research
1998-2001
Activation-induced cytidine deaminase (AID) initiates secondary antibody diversification processes by deaminating cytidines on single-stranded DNA. AID preferentially mutates preceded W(A/T)R(A/G) dinucleotides, a sequence specificity that is evolutionarily conserved from bony fish to humans. To uncover the biochemical mechanism of AID, we compared catalytic and binding kinetics WRC (a hot-spot motif, where W equals A or T R G) non-WRC motifs. We show although purified deaminates over motifs...
Significance The enzyme activation-induced deaminase (AID) triggers antibody class switch recombination (CSR), a critical mechanism for immune response. CSR is an intrachromosomal rearrangement requiring DNA double strand breaks that are initiated by AID and must be repaired specific repair pathways. We identify domain of required to link the damage step with subsequent during as well chromosomal translocations, collateral effect CSR. influences recruitment appropriate end-joining pathways...
Protoporphyrin IX (PpIX) is an endogenous fluorescent molecule that selectively accumulates in cancer cells treated with the heme precursor 5-aminolevulinic acid (5-ALA).This cancer-specific accumulation of PpIX used to distinguish tumor from normal tissues fluorescence-guided surgery (FGS) and destroy by photodynamic therapy (PDT).In this study, we demonstrate oncogenic Ras/mitogen-activated protein kinase (MEK) pathway can modulate cells.Methods: To identify Ras downstream elements...
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...
Due to constitutive expression in cells targeted by human immunodeficiency virus (HIV), and immediate mode of viral restriction upon HIV entry into the host cell, APOBEC3G (A3G) APOBEC3F (A3F) have been considered primarily as agents innate immunity. Recent bioinformatic mouse model studies hint at possibility that mutation genome these enzymes may also affect adaptive immunity but whether this occurs HIV-infected individuals has not examined. We evaluated APOBEC-mediated mutations within...
The evolutionary arms race between host restriction factors and viral antagonists provides crucial insights into immune system evolution adaptation. This study investigates the structural dynamics of double-domain A3F A3G their inhibitor, Vif, across diverse primate species. By constructing 3D homology models integrating ancestral sequence reconstruction (ASR), we identified patterns diversity, conservation, functional Inactive CD1 (Catalytic Domain 1) domains displayed greater diversity...
Activation-induced cytidine deaminase (AID) initiates antibody diversification processes by deaminating immunoglobulin sequences. Since transcription of target genes is required for deamination in vivo and AID exclusively mutates single-stranded DNA (ssDNA) vitro, has been postulated to mutate bubbles. However, since ssDNA generated can assume multiple structures, it unknown which these are targeted vivo. Here we examine the enzymatic binding properties different structures. We report that...
Mismatch repair plays an essential role in reducing the cellular mutation load. Paradoxically, proteins this pathway produce A·T mutations during somatic hypermutation of immunoglobulin genes. Although recent evidence implicates translesional DNA polymerase η producing these mutations, it is unknown how or other polymerases are recruited to genes, since enzymes not normally utilized conventional mismatch repair. In report, we demonstrate that were closely associated with transversion at a...
Cytidine deaminases of the AID/APOBEC family catalyze C-to-U nucleotide transitions in mRNA or DNA. Members APOBEC3 branch are involved antiviral defense, whereas AID contributes to diversification antibody repertoires jawed vertebrates via somatic hypermutation, gene conversion, and class switch recombination. In extant jawless vertebrate, lamprey, two members implicated generation diversity variable lymphocyte receptors (VLRs). Expression studies linked CDA1 CDA2 genes assembly VLRA/C...
APOBEC3, an enzyme subfamily that plays a role in virus restriction by generating mutations at particular DNA motifs or mutational 'hotspots', can drive viral mutagenesis with host-specific preferential hotspot contributing to pathogen variation. While previous analysis of genomes from the 2022 Mpox (formerly Monkeypox) disease outbreak has shown high frequency C>T TC motifs, suggesting recent are human APOBEC3-mediated, how emerging monkeypox (MPXV) strains will evolve as consequence...
Activation-induced cytidine deaminase (AID) deaminates deoxycytidine (dC) to deoxyuracil (dU) at immunoglobulin loci in B lymphocytes mediate secondary antibody diversification. Recently, AID has been proposed also epigenetic reprogramming by demethylating methylated cytidines (mC) possibly through deamination. overexpression zebrafish embryos was shown promote genome demethylation G:T lesions, implicating a deamination-dependent mechanism. We and others have previously that mC is poor...
Activation-induced cytidine deaminase (AID) is a genome-mutating enzyme that initiates class switch recombination and somatic hypermutation of antibodies in jawed vertebrates. We previously described the biochemical properties human AID found it an unusual exhibits binding affinities for its substrate DNA catalytic rates several orders magnitude higher lower, respectively, than typical enzyme. Recently, we solved functional structure demonstrated these are due to nonspecific on surface,...
Activation-induced cytidine deaminase (AID) initiates antibody diversification by mutating immunoglobulin loci in B lymphocytes. AID and related APOBEC3 (A3) enzymes also induce genome-wide mutations lesions implicated tumorigenesis tumor progression. The most prevalent mutation signatures across diverse genomes are attributable to the mistargeted mutagenic activities of AID/A3s. Thus, inhibiting AID/A3s has been suggested be therapeutic benefit. We previously used a...