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Harold E. Smith
National Institutes of Health
GeneMolecular biologyCaenorhabditis elegansGeneticsBiology
31Publications
12H-index
1,211Citations
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Publications 34
Newest
#1Nirajan Bhandari (UD: University of Delaware)H-Index: 1
#2Christine Rourke (UD: University of Delaware)
Last. Aimee Jaramillo-Lambert (UD: University of Delaware)
view all 9 authors...
Topoisomerase II is an enzyme with important roles in chromosome biology. This enzyme relieves supercoiling and DNA and RNA entanglements generated during mitosis. Recent studies have demonstrated that Topoisomerase II is also involved in the segregation of homologous chromosomes during the first meiotic division. However, the function and regulation of Topoisomerase II in meiosis has not been fully elucidated. Here, we conducted a genetic suppressor screen in Caenorhabditis elegans to identify ...
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#1Sharvani Mahadevaraju (NIH: National Institutes of Health)
#2Justin M. Fear (NIH: National Institutes of Health)H-Index: 10
Last. Zelalem Demere (JHUSOM: Johns Hopkins University School of Medicine)
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Sex chromosome gene content and expression is unusual. In many organisms, the X and Y chromosomes are inactivated in spermatocytes, possibly as a defense mechanism against insertions into unpaired chromatin. In addition to current sex chromosomes, Drosophila has a small gene-poor X-chromosome relic (4th) that re-acquired autosomal status. Using single-cell RNA-Seq, we demonstrate that the single X and pair of 4th chromosomes are specifically inactivated in primary spermatocytes. In contrast, gen...
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#1Hye-Kyung Lee (NIH: National Institutes of Health)H-Index: 13
#2Harold E. Smith (NIH: National Institutes of Health)H-Index: 12
Last. Lothar Hennighausen (NIH: National Institutes of Health)H-Index: 89
view all 5 authors...
Deaminase base editing has emerged as a tool to install or correct point mutations in the genomes of living cells in a wide range of organisms. However, the genome-wide off-target effects introduced by base editors in the mammalian genome have been examined in only one study. Here, we have investigated the fidelity of cytosine base editor 4 (BE4) and adenine base editors (ABE) in mouse embryos using unbiased whole-genome sequencing of a family-based trio cohort. The same sgRNA was used for BE4 a...
3 CitationsSource
#1Hye-Kyung Lee (NIH: National Institutes of Health)H-Index: 13
#2Harold E. Smith (NIH: National Institutes of Health)H-Index: 12
Last. Lothar Hennighausen (NIH: National Institutes of Health)H-Index: 89
view all 5 authors...
Deaminase base editing has emerged as a tool to install or correct point mutations in the genomes of living cells in a wide range of organisms and its ultimate success therapeutically depends on its accuracy. Here we have investigated the fidelity of cytosine base editor 4 (BE4) and adenine base editor (ABE) in mouse embryos using unbiased whole genome sequencing of a family-based trio cohort. We demonstrate that BE4-edited mice carry an excess of single-nucleotide variants and deletions compare...
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#1Hye-Kyung Lee (NIH: National Institutes of Health)H-Index: 13
#2Michaela Willi (NIH: National Institutes of Health)H-Index: 8
Last. Lothar Hennighausen (NIH: National Institutes of Health)H-Index: 89
view all 7 authors...
A particular challenge in genome engineering has been the simultaneous introduction of mutations into linked (located on the same chromosome) loci. Although CRISPR/Cas9 has been widely used to mutate individual sites, its application in simultaneously targeting of linked loci is limited as multiple nearby double-stranded DNA breaks created by Cas9 routinely result in the deletion of sequences between the cleavage sites. Base editing is a newer form of genome editing that directly converts C∙G-to...
3 CitationsSource
#1Michaela Willi (NIH: National Institutes of Health)H-Index: 8
#2Harold E. Smith (NIH: National Institutes of Health)H-Index: 12
Last. Lothar Hennighausen (NIH: National Institutes of Health)H-Index: 89
view all 5 authors...
9 CitationsSource
#1Jack R. Davison (NIH: National Institutes of Health)H-Index: 6
#2Katheryn Lohith (NIH: National Institutes of Health)H-Index: 4
Last. Carole A. Bewley (NIH: National Institutes of Health)H-Index: 40
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ABSTRACT The permeation of antibiotics through bacterial membranes to their target site is a crucial determinant of drug activity but in many cases remains poorly understood. During screening efforts to discover new broad-spectrum antibiotic compounds from marine sponge samples, we identified a new analog of the peptidyl nucleoside antibiotic blasticidin S that exhibited up to 16-fold-improved potency against a range of laboratory and clinical bacterial strains which we named P10. Whole-genome s...
1 CitationsSource
#1Tetsunari Fukushige (NIH: National Institutes of Health)H-Index: 19
#2Harold E. Smith (NIH: National Institutes of Health)H-Index: 12
Last. John A. Hanover (NIH: National Institutes of Health)H-Index: 56
view all 5 authors...
Oxidative damage contributes to human diseases of aging including diabetes, cancer, and cardiovascular disorders. Reactive oxygen species resulting from xenobiotic and endogenous metabolites are sensed by a poorly understood process, triggering a cascade of regulatory factors and leading to the activation of the transcription factor Nrf2 (Nuclear factor-erythroid-related factor 2, SKN-1 in Caenorhabditis elegans ). Nrf2/SKN-1 activation promotes the induction of the phase II detoxification syste...
3 CitationsSource
#1Hye-Kyung Lee (SNU: Seoul National University)H-Index: 13
#2Michaela Willi (Innsbruck Medical University)H-Index: 8
Last. Lothar Hennighausen (NIH: National Institutes of Health)H-Index: 89
view all 7 authors...
11 CitationsSource
#1Harold E. Smith (NIH: National Institutes of Health)H-Index: 12
#2Sijung Yun (NIH: National Institutes of Health)H-Index: 5
Whole-genome sequencing is a powerful tool for analyzing genetic variation on a global scale. One particularly useful application is the identification of mutations obtained by classical phenotypic screens in model species. Sequence data from the mutant strain is aligned to the reference genome, and then variants are called to generate a list of candidate alleles. A number of software pipelines for mutation identification have been targeted to C. elegans, with particular emphasis on ease of use,...
5 CitationsSource
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