Institution
Kettering University
Education•Flint, Michigan, United States•
About: Kettering University is a education organization based out in Flint, Michigan, United States. It is known for research contribution in the topics: RNA & Antigen. The organization has 6842 authors who have published 7689 publications receiving 337503 citations. The organization is also known as: GMI Engineering & Management Institute & General Motors Institute.
Topics: RNA, Antigen, DNA, Cancer, Population
Papers published on a yearly basis
Papers
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TL;DR: Specific DSBs are created in mouse chromosomes for the first time, using an expression system for a rare-cutting endonuclease, I-SceI, and are apparently recombinogenic, stimulating gene targeting of a homologous fragment by more than 2 orders of magnitude.
Abstract: To maintain genomic integrity, double-strand breaks (DSBs) in chromosomal DNA must be repaired. In mammalian systems, the analysis of the repair of chromosomal DSBs has been limited by the inability to introduce well-defined DSBs in genomic DNA. In this study, we created specific DSBs in mouse chromosomes for the first time, using an expression system for a rare-cutting endonuclease, I-SceI. A genetic assay has been devised to monitor the repair of DSBs, whereby cleavage sites for I-SceI have been integrated into the mouse genome in two tandem neomycin phosphotransferase genes. We find that cleavage of the I-SceI sites is very efficient, with at least 12% of stably transfected cells having at least one cleavage event and, of these, more than 70% have undergone cleavage at both I-SceI sites. Cleavage of both sites in a fraction of clones deletes 3.8 kb of intervening chromosomal sequences. We find that the DSBs are repaired by both homologous and nonhomologous mechanisms. Nonhomologous repair events frequently result in small deletions after rejoining of the two DNA ends. Some of these appear to occur by simple blunt-ended ligation, whereas several others may occur through annealing of short regions of terminal homology. The DSBs are apparently recombinogenic, stimulating gene targeting of a homologous fragment by more than 2 orders of magnitude. Whereas gene-targeted clones are nearly undetectable without endonuclease expression, they represent approximately 10% of cells transfected with the I-SceI expression vector. Gene targeted clones are of two major types, those that occur by two-sided homologous recombination with the homologous fragment and those that occur by one-sided homologous recombination. Our results are expected to impact a number of areas in the study of mammalian genome dynamics, including the analysis of the repair of DSBs and homologous recombination and, potentially, molecular genetic analyses of mammalian genomes.
848 citations
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TL;DR: It is shown that stage I lung adenocarcinoma lesions already harbor significantly altered T cell and NK cell compartments, andaired single-cell analyses thus offer valuable knowledge of tumor-driven immune changes, providing a powerful tool for the rational design of immune therapies.
838 citations
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TL;DR: The existence of well-conserved mammalian mirtrons indicates their relatively ancient incorporation into endogenous regulatory pathways, and it is hypothesized that different animals may have independently evolved the capacity for this hybrid small RNA pathway.
827 citations
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TL;DR: The specificity for peptide ligands is investigated using a set of peptides of random sequence but defined chain length and selects for aliphatic residues and accommodates them in an environment energetically equivalent to the interior of a folded protein.
Abstract: Members of the heat-shock protein family (hsp70s) can distinguish folded from unfolded proteins. This property is crucial to the role of hsp70s as molecular chaperones and is attributable to the amino-acid specificity of the peptide-binding site. The specificity for peptide ligands is investigated using a set of peptides of random sequence but defined chain length. The peptide-binding site selects for aliphatic residues and accommodates them in an environment energetically equivalent to the interior of a folded protein.
818 citations
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TL;DR: It is shown here that mouse embryos that lack both Ift172 and Smo are identical to IFT172 single mutants, which indicates that Ift 172 acts downstream of Smo, which means that IFT mutants have a weaker neural patterning phenotype than Smo mutants.
Abstract: The intraflagellar transport (IFT) proteins Ift172/Wimple and Polaris/Ift88 and the anterograde IFT motor kinesin-II are required for the production and maintenance of cilia. These proteins are also required for the activation of targets of the mouse Hedgehog (Hh) pathway by Gli transcription factors. The phenotypes of the IFT mutants, however, are not identical to mutants that lack Smoothened (Smo), an essential activator of the Hh pathway. We show here that mouse embryos that lack both Ift172 and Smo are identical to Ift172 single mutants, which indicates that Ift172 acts downstream of Smo. Ift172 mutants have a weaker neural patterning phenotype than Smo mutants, because Ift172, but not Smo, is required for proteolytic processing of Gli3 to its repressor form. Dnchc2 and Kif3a, essential subunits of the retrograde and anterograde IFT motors, are also required for both formation of Gli activator and proteolytic processing of Gli3. As a result, IFT mutants display a loss of Hh signaling phenotype in the neural tube, where Gli activators play the major role in pattern formation, and a gain of Hh signaling phenotype in the limb, where Gli3 repressor plays the major role. Because both anterograde and retrograde IFT are essential for positive and negative responses to Hh, and because cilia are present on Hh responsive cells, it is likely that cilia act as organelles that are required for all activity of the mouse Hh pathway.
799 citations
Authors
Showing all 6853 results
Name | H-index | Papers | Citations |
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Joan Massagué | 189 | 408 | 149951 |
Chris Sander | 178 | 713 | 233287 |
Timothy A. Springer | 167 | 669 | 122421 |
Murray F. Brennan | 161 | 925 | 97087 |
Charles M. Rice | 154 | 561 | 83812 |
Lloyd J. Old | 152 | 775 | 101377 |
Howard I. Scher | 151 | 944 | 101737 |
Paul Tempst | 148 | 309 | 89225 |
Pier Paolo Pandolfi | 146 | 529 | 88334 |
Barton F. Haynes | 144 | 911 | 79014 |
Jedd D. Wolchok | 140 | 713 | 123336 |
James P. Allison | 137 | 483 | 83336 |
Harold E. Varmus | 137 | 496 | 76320 |
Scott W. Lowe | 134 | 396 | 89376 |
David S. Klimstra | 133 | 564 | 61682 |