- Genetic factors in colorectal cancer
- Fungal and yeast genetics research
- DNA Repair Mechanisms
- PARP inhibition in cancer therapy
- RNA and protein synthesis mechanisms
- Toxin Mechanisms and Immunotoxins
- Genomics and Phylogenetic Studies
- Antimicrobial Resistance in Staphylococcus
- Digestive system and related health
- Molecular Biology Techniques and Applications
- Cellular Mechanics and Interactions
- Colorectal Cancer Screening and Detection
- Cancer, Hypoxia, and Metabolism
- Diamond and Carbon-based Materials Research
- Microbial Metabolism and Applications
- Plant tissue culture and regeneration
- Animal Genetics and Reproduction
- Advancements in PLL and VCO Technologies
- Microbial Metabolic Engineering and Bioproduction
- Carcinogens and Genotoxicity Assessment
- CRISPR and Genetic Engineering
- PI3K/AKT/mTOR signaling in cancer
- Bacterial Genetics and Biotechnology
- Cellular transport and secretion
- Fungal Plant Pathogen Control
Harvard University
1995-2024
Brigham and Women's Hospital
2024
University of Pennsylvania
2006
Howard Hughes Medical Institute
2006
University of Missouri–Kansas City
2006
Whitehead Institute for Biomedical Research
2006
Longwood University
2003
Dana-Farber Cancer Institute
1996-1999
Cancer Genetics (United States)
1996-1999
Sidney Kimmel Cancer Center
1996
Alpha-synuclein (alphaSyn) misfolding is associated with several devastating neurodegenerative disorders, including Parkinson's disease (PD). In yeast cells and in neurons alphaSyn accumulation cytotoxic, but little known about its normal function or pathobiology. The earliest defect following expression was a block endoplasmic reticulum (ER)-to-Golgi vesicular trafficking. genomewide screen, the largest class of toxicity modifiers were proteins functioning at this same step, Rab guanosine...
Saccharomyces cerevisiae encodes six genes, MSH1-6, which encode proteins related to the bacterial MutS protein. In this study role of MSH2, MSH3, and MSH6 in mismatch repair has been examined by measuring rate accumulating mutations mutation spectrum strains containing different combinations msh2, msh3, msh6 studying physical interaction between MSH2 protein MSH3 proteins. The results indicate that S. two pathways MSH2-dependent repair: one recognized single-base mispairs requires MSH6, a...
The genetic and biochemical properties of three human MutS homologues, hMSH2, hMSH3, hMSH6, have been examined. full-length hMSH6 cDNA genomic locus were isolated characterized, it was demonstrated that the gene consisted 10 exons mapped to chromosome 2p15-16. hMSH3 in some cases found contain a 27-bp deletion resulting loss nine amino acids, depending on individual from which isolated. all showed similar tissue-specific expression patterns. hMSH2 protein formed complex with both proteins,...
Sequence similarities between the enzymatic region of poly-ADP-ribose polymerase and corresponding mono-ADP-ribosylating bacterial toxins suggest in active site structure catalytic mechanism. Glu988 human aligns with glutamic acid toxins, replacement this residue Gln, Asp, or Ala caused major reductions synthesis enzyme-linked poly-ADP-ribose. Replacement any 3 other nearby Glu residues had little effect. The mutations produced similar changes activity carboxyl-terminal 40-kDa fragment fused...
The availability of an annotated genome sequence for the yeast Saccharomyces cerevisiae has made possible proteome-scale study protein function and protein–protein interactions. These studies rely on cloned open reading frame (ORF) collections that can be used cell-free or cell-based expression. Several ORF are available, but their use data interpretation hindered by reliance now out-of-date annotations, inflexible presence N- C-terminal tags, and/or unknown mutations introduced during...
The interaction of the <i>Saccharomyces cerevisiae</i> MSH2-MSH6 complex with mispaired bases was analyzed using gel mobility shift assays and surface plasmon resonance methods. Under equilibrium binding conditions, bound to homoduplex DNA a <i>K</i><sub>d</sub> 3.9 nm oligonucleotide duplexes containing T:G, +1, +2, +4, +10 insertion/deletion loop (IDL) mispairs <i>K</i><sub>d</sub>values 0.20, 0.25, 11, 3.2, 0.55 nm, respectively. Competition experiments 65 different substrates revealed...
Intestinal epithelia express two long myosin light chain kinase (MLCK) splice variants, MLCK1 and MLCK2 that differ by the absence of a complete immunoglobulin-like (Ig) domain 3 within MLCK2. Only is associated with perijunctional actomyosin ring at steady state, this localization enhanced inflammatory stimuli including tumor necrosis factor (TNF). Here we sought to identify domains direct their relevance disease. Ileal biopsies from Crohn's disease patients demonstrated preferential...
Genetic and biochemical studies have indicated that mismatch repair proteins can interact with recombination intermediates. In this study, gel shift assays electron microscopic analysis were used to show the <i>Saccharomyces cerevisiae</i> MSH2/6 complex binds Holliday junctions has an affinity specificity for them is at least as high it mispaired bases. Under equilibrium binding conditions, had a <i>K</i> <sub>d</sub> of 0.5 nm. The enhanced cleavage by T4 endonuclease VII T7 I. This...
Abstract The mechanism of elongation poly(ADP-ribose) on polymerase was examined in two ways. first technique involved a pulse-chase protocol. Poly(ADP-ribose) labeled with radioactive NAD, excess precursor removed by rapid gel filtration chromatography, and nonradioactive NAD supplied for second incubation. products were released alkali digested venom phosphodiesterase which generates AMP uniquely from the distal terminus. residue that during pulse remained at terminus not converted to an...