A5000026759- DNA Repair Mechanisms
- CRISPR and Genetic Engineering
- Genomics and Chromatin Dynamics
- Carcinogens and Genotoxicity Assessment
- Chromosomal and Genetic Variations
- Genetics, Aging, and Longevity in Model Organisms
- DNA and Nucleic Acid Chemistry
- Plant Genetic and Mutation Studies
- RNA Research and Splicing
- Animal Nutrition and Physiology
- Microtubule and mitosis dynamics
- Genetically Modified Organisms Research
- Insect and Pesticide Research
- Epigenetics and DNA Methylation
- Fungal and yeast genetics research
- Genetic factors in colorectal cancer
- Nuclear Structure and Function
- Education and Critical Thinking Development
- Animal Behavior and Reproduction
- Mitochondrial Function and Pathology
- Genomics and Phylogenetic Studies
- Advanced biosensing and bioanalysis techniques
- Innovative Teaching Methods
- Cancer therapeutics and mechanisms
- Reproductive Biology and Fertility
Tufts University
2016-2025
University of Southern California
2023
Mount St. Mary's University
2014
Spire Corporation (United States)
2003-2007
University of North Carolina at Chapel Hill
2001-2004
Massachusetts Institute of Technology
1999-2001
University of Colorado Boulder
2000
Matt Kaeberlein, Mitch McVey, and Leonard Guarente Department of Biology, Massachusetts Institute Technology, Cambridge, 02139 USA
Bloom syndrome, characterized by a predisposition to cancer, is caused mutation of the RecQ DNA helicase gene BLM. The precise function BLM remains unclear. Previous research suggested that Drosophila functions in repair double-strand breaks. Most breaks flies are repaired homologous recombination through synthesis-dependent strand-annealing pathway. Here, we demonstrate mutants severely impaired their ability carry out synthesis during strand annealing. Consequently, completed error-prone...
DNA double-strand breaks are repaired by multiple mechanisms that roughly grouped into the categories of homology-directed repair and non-homologous end joining. End-joining can be further classified as either classical joining, which requires ligase 4, or "alternative" does not. Alternative joining has been associated with genomic deletions translocations, but its molecular mechanism(s) largely uncharacterized. Here, we report Drosophila melanogaster polymerase theta (pol theta), encoded...
Ku or DNA ligase 4-independent alternative end joining (alt-EJ) repair of double-strand breaks (DSBs) frequently correlates with increased junctional microhomology. However, alt-EJ also produces junctions without microhomology (apparent blunt joins), and the exact role in both classical non-homologous (NHEJ) remains unclear. To better understand degree to which depends on annealing at pre-existing microhomologies, we examined inaccurate an I-SceI DSB lacking nearby microhomologies greater...
Small insertions and deletions (indels) large structural variations (SVs) are major contributors to human genetic diversity disease. However, mutation rates characteristics of de novo indels SVs in the general population have remained largely unexplored. We report 332 validated changes identified whole genomes 250 families, including complex indels, retrotransposon insertions, interchromosomal events. These data indicate a rate 2.94 (1–20 bp) 0.16 (>20 per generation. De affect on average...
Abstract DNA double-strand breaks (DSBs), a major source of genome instability, are often repaired through homologous recombination pathways. Models for these pathways have been proposed, but the precise mechanisms and rules governing their use remain unclear. In Drosophila, synthesis-dependent strand annealing (SDSA) model can explain most DSB repair. To investigate SDSA, we induced DSBs by excision P element from male X chromosome, which produces 14-kb gap relative to sister chromatid....
Abstract Bloom Syndrome, a rare human disorder characterized by genomic instability and predisposition to cancer, is caused mutation of BLM, which encodes RecQ-family DNA helicase. The Drosophila melanogaster ortholog DmBlm, encoded mus309. Mutations in mus309 cause hypersensitivity DNA-damaging agents, female sterility, defects repairing double-strand breaks (DSBs). To better understand these phenotypes, we isolated novel alleles. that delete the N terminus but not helicase domain, have DSB...
This study investigated student learning outcomes using a case-based approach focused on cellular respiration. Students who used the case study, relative to students did not use exhibited significantly greater gain, and demonstrated of higher-order thinking skills. Preliminary data indicate that after engaging with were more likely answer question addressing misconceptions about respiration correctly when compared study. More rigorous testing is needed fully elucidate whether can effectively...
Double strand breaks (DSBs) and interstrand crosslinks (ICLs) are toxic DNA lesions that can be repaired through multiple pathways, some of which involve shared proteins. One these proteins, Polymerase θ (Pol θ), coordinates a mutagenic DSB repair pathway named microhomology-mediated end joining (MMEJ) is also critical component for bypass or ICLs in several organisms. Pol contains both polymerase helicase-like domains tethered by an unstructured central region. While the role domain...
Abstract Evidence from many organisms indicates that the conserved RecQ helicases function in maintenance of genomic stability. Mutation SGS1 and WRN, which encode homologues budding yeast humans, respectively, results phenotypes characteristic premature aging. SRS2, another DNA helicase, causes synthetic slow growth an sgs1 background. In this work, we demonstrate srs2 mutants have a shortened life span similar to mutants. Further dissection survival curves reveals two distinct phenomena. A...
Abstract Repair of DNA double-strand breaks can occur by either nonhomologous end joining or homologous recombination. Most requires a specialized ligase, ligase IV (Lig4). In Drosophila melanogaster, created excision P element are usually repaired recombination pathway called synthesis-dependent strand annealing (SDSA). SDSA invasion mediated DmRad51, the product spn-A gene. mutants, repair proceeds through nonconservative involving microhomologies found within 17-nt overhangs produced...
Bloom syndrome is a rare disorder associated with cancer predisposition and genomic instability caused by loss of the RecQ helicase BLM. The Drosophila ortholog BLM (DmBlm) required for accurate repair DNA double-strand gaps homologous recombination. Repair products from DmBlm mutants have shorter synthesis tract lengths compared to wild type are frequently deletions flanking break site. To determine mechanisms responsible deletion formation in absence DmBlm, we characterized after excision...
In metazoans, the mechanism by which DNA is synthesized during homologous recombination repair of double-strand breaks poorly understood. Specifically, identities polymerase(s) that carry out synthesis and how they are recruited to sites unclear. Here, we have investigated roles several different polymerases in Drosophila melanogaster. Using a gap assay, found impaired lacking polymerase zeta and, lesser extent, eta. addition, Pol32 protein, part delta complex, needed for requiring extensive...
Alternative end-joining (alt-EJ) repair of DNA double-strand breaks is associated with deletions, chromosome translocations, and genome instability. Alt-EJ frequently uses annealing microhomologous sequences to tether broken ends. When accessible pre-existing microhomologies do not exist, we have postulated that new can be created via limited synthesis at secondary-structure forming sequences. This model, called synthesis-dependent microhomology-mediated end joining (SD-MMEJ), predicts...
Abstract A hallmark of the vertebrate stress response is a rapid increase in glucocorticoids and catecholamines; however, this does not mean that these mediators are best, or should be only, metric measured when studying stress. Instead, it becoming increasingly clear assaying suite downstream metrics necessary physiology. One component could assessing double‐stranded DNA damage (dsDNA damage), which has recently been shown to blood with both acute chronic house sparrows ( Passer domesticus...