[October 19, 2006] Findings from Massachusetts Institute of Technology, U.S., advance knowledge in DNA research Tweet (Science Letter Via Thomson Dialog NewsEdge) Reports from Massachusetts Institute of Technology, U.S., highlight recent research in DNA. Study 1: DNA damage during replication can induce transcriptional responses that help bacteria survive. Researchers from the United States reported, "DNA damage and perturbations in DNA replication can induce global transcriptional responses that can help organisms repair the damage and survive. RecA is known to mediate transcriptional responses to DNA damage in several bacterial species by inactivating the repressor LexA and phage repressors." "To gain insight into how Bacillus subtilis responds to various types of DNA damage, we measured the effects of DNA damage and perturbations in replication on mRNA levels by using DNA microarrays," described A.I. Goranov and colleagues, Massachusetts Institute of Technology (MIT). "We perturbed replication either directly with p-hydroxyphenylazo-uracil (HPUra), an inhibitor of DNA polymerase, or indirectly with the DNA-damaging reagents mitomycin C (MMC) and UV irradiation." They noted, "Our results indicate that the transcriptional responses to HPUra, MMC, and UV are only partially overlapping. recA is the major transcriptional regulator under all of the tested conditions, and LexA appears to directly repress the expression of 63 genes in 26 operons, including the 18 operons previously identified as LexA targets. MMC and HPUra treatments caused induction of an integrative and conjugative element (ICEBs1) and resident prophages (PBSX and SP beta), which affected the expression of many host genes." "Consistent with previous results," the authors continued, "the induction of these mobile elements required recA. Induction of the phage appeared to require inactivation of LexA. Unrepaired UV damage and treatment with MMC also affected the expression of some of the genes that are controlled by DnaA. Furthermore, MMC treatment caused an increase in origin-proximal gene dosage." "Our results," they concluded, "indicate that different types of DNA damage have different effects on replication and on the global transcriptional profile." Goranov and colleagues published their study in the Journal of Bacteriology (Characterization of the global transcriptional responses to different types of DNA damage and disruption of replication in Bacillus subtilis. J Bacteriol, 2006;188(15):5595-5605). For additional information, contact A.D. Grossman, MIT, Dept. of Biology, Bldg 68-530, Cambridge, MA 02139, USA. Study 2: Scientists characterize poly (beta amino ester) microparticles for genetic vaccine delivery in a recent issue of the Journal of Controlled Release. "Microparticulate delivery systems are a promising and versatile enhancement to DNA vaccines because they can target large payloads of plasmid and immunomodulating materials to antigen presenting cells (APC)." "A pH sensitive poly-beta amino ester (PBAE) has been recently described which substantially increases adjuvancy and delivery efficiency of such microparticle formulations. This work describes the characterization and formulation considerations specific to these PBAE containing microparticles," investigators in the United States report. "PBAE increases the supercoiled content and overall effective loading of plasmid DNA," said Steven R. Little and colleagues at the Massachusetts Institute of Technology and the University of Wisconsin-Madison. "This polymer also significantly buffers the pH micro-environment created by ester bond degradation, rendering encapsulated plasmid more suitable for transfection. Release of plasmid from microparticles is controllable based on the amount of PBAE in the composition. Transfection is dependant upon phagocytosis, and is optimal for 15% and 25% PBAE microparticle formulations." Little and his collaborators reported, "However, larger quantities of PBAE may be toxic to cells indicating that the 15% PBAE formulation is a suitable candidate for delivery in future studies with disease-specific DNA vaccines." Little and his coauthors published their study in the Journal of Controlled Release (Formulation and characterization of poly (beta amino ester) microparticles for genetic vaccine delivery. J Control Release, 2005;107(3):449-462). For additional information, contact Robert Langer, Department of Chemical Engineering, Massachusetts Institute of Technology, 45 Carleton Street, Building E25, Room 342, Cambridge, MA 02142, USA. [email protected]. Study 3: Intragenic tandem repeats generate functional variability in pathogens. "Tandemly repeated DNA sequences are highly dynamic components of genomes(1). Most repeats are in intergenic regions, but some are in coding sequences or pseudogenes(2)," researchers in the United States report. "In humans, expansion of intragenic triplet repeats is associated with various diseases, including Huntington chorea and fragile X syndrome(3,4). The persistence of intragenic repeats in genomes suggests that there is a compensating benefit," predicted K.J. Verstrepen and colleagues, Massachusetts Institute of Technology. "Here we show," the scientists continued, "that in the genome of Saccharomyces cerevisiae, most genes containing intragenic repeats encode cell-wall proteins. The repeats trigger frequent recombination events in the gene or between the gene and a pseudogene, causing expansion and contraction in the gene size. This size variation creates quantitative alterations in phenotypes (e. g., adhesion, flocculation or biofilm formation)." "We propose," they concluded, "that variation in intragenic repeat number provides the functional diversity of cell surface antigens that, in fungi and other pathogens, allows rapid adaptation to the environment and elusion of the host immune system." Verstrepen and colleagues published their study in Nature Genetics (Intragenic tandem repeats generate functional variability. Nat Genet, 2005;37(9):986-990). For additional information, contact G.R. Fink, Massachusetts Institute of Technology, Whitehead Institute Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA. Keywords: Cambridge, Massachusetts, United States, DNA Research, DNA Sequence Proteomics, Deoxyribonucleic Acid, Fragile X Syndrome, Genetics, Immunology, Saccharomyces cerevisiae, Intragenic Repeat, Genome, Pseudogene, Phenotype. This article was prepared by Science Letter editors from staff and other reports. Copyright 2006, Science Letter via NewsRx.com. 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