Mouse anti-Human DNA Topoisomerase I monoclonal antibody, clone D-32

Saccharomyces cerevisiae sir2 Delta or top1 Delta mutants exhibit similar phenotypes involving ribosomal DNA, including (i) loss of transcriptional silencing, resulting in non-coding RNA hyperproduction from cryptic RNA polymerase II promoters; (ii) alterations in recombination; and (iii) a general increase in histone acetylation. Given the distinct enzymatic activities of Sir2 and Tool proteins, a histone deacetylase and a DNA topoisomerase, respectively, we investigated whether genetic and/or physical interactions between the two proteins could explain the shared ribosomal RNA genes (rDNA) phenotypes. We employed an approach of complementing top1 Delta cells with yeast, human, truncated, and chimeric yeast/human TOP1 constructs and of assessing the extent of non-coding RNA silencing and histone H4K16 deacetylation. Our findings demonstrate that residues 115-125 within the yeast Top1p N-terminal domain are required for the complementation of the top1 Delta rDNA phenotypes. In chromatin immunoprecipitation and co-immunoprecipitation experiments, we further demonstrate the physical interaction between Top1p and Sir2p. Our genetic and biochemical studies support a model whereby Top1p recruits Sir2p to the rDNA and clarifies a structural role of DNA topoisomerase I in the epigenetic regulation of rDNA, independent of its known catalytic activity. (C) 2016 Elsevier Ltd. All rights reserved.

Five new formyl phloroglucinol meroterpenoids (FPMs), eucalteretials A-E (1-5), along with eight known analogues (6-13), were isolated from the twigs and leaves of Eucalyptus tereticornis. Their structures were established mainly by analysis of comprehensive spectroscopic data, and their absolute configurations were determined by electron circular dichroism (ECD) calculation. Within FPMs, both 1 and 2 are rare adducts of formyl phloroglucinol moiety and germacrene unit with different coupling patterns, respectively. Compound 3 exhibited significant cytotoxicity against HCT116 cell line with an IC50 value of 4.76 M. In addition, 5 and 9 were proved to be rare topoisomerase I (Top1) inhibitors. (C) 2018 Elsevier Ltd. All rights reserved.