Showing papers by "Carl W. Schmid published in 1996"
TL;DR: This paper presents a probabilistic analysis of the H2O2 gene that was constructed at the Lawrence Livermore National Laboratory during the 1990s as well as a comparison study conducted at the University of California at Davis in 2011.
Abstract: 1 Human Genome Center, L-452, Biology and Biotechnology Research Program, Lawrence Livermore National Laboratory, P.O. Box 808, Livermore, CA 94551, USA 2 Department of Biochemistry and Molecular Biology, Center for Human and Molecular Genetics, Louisiana State University Medical Center, 1901 Perdido St., New Orleans, LA 70112, USA 3 Department of Chemistry, University of California at Davis, Davis, CA 95616, USA 4 Linus Pauling Institute of Science and Medicine, 440 Page Mill Road, Palo Alto, CA 94306, USA 5 Centre de Recherche, Hopital Ste-Justine, Departement de Pediatrie, Universite de Montreal, Montreal, Quebec, Canada H3T 1C5 6 Section of Molecular and Cell Biology, University of California at Davis, Davis, CA 95616, USA 7 Institute of Molecular Medical Sciences, 460 Page Mill Road, Palo Alto, CA 94306, USA
284 citations
TL;DR: This chapter focuses on Alu repeats, a young Alu subfamily that appeared by simple drift of its founder, providing a model for the continual turnover of active repeat-sequence families.
Abstract: Publisher Summary Human repeats have been largely identified and cataloged, accounting for a substantial fraction of the genome. Repetitive sequences are ubiquitously interspersed with single-copy sequences throughout the genome. Interspersed repeats are largely composed of only four distinct families (Alu, LINE 1, MIR, and MaLR), which together comprise 10 to 15% of the entire genome. Alu and LINE 1 subfamilies of different evolutionary ages have different degrees of retrotranspositional activity. This chapter focuses on Alu repeats. Although Alus exemplify many properties of both human and nonhuman repeats, their amplification raises unsolved problems in retroposition. A young Alu subfamily appeared by simple drift of its founder, providing a model for the continual turnover of active repeat-sequence families. Repetitive sequences, ubiquitously distributed throughout the genome, cause various genetic effects. Unequal crossing-over among interspersed repeats duplicates or deletes sequences, thereby, mutating genes. Ubiquitous, homologous repeats, such as Alu, might serve as frequent sites for unequal homologous crossing-over, consequently scrambling their flanking direct repeats.. Unequal Alu–Alu crossing-over duplicates, deletes, or scrambles genetic information. Alu–Alu crossing-over within the low-density lipoprotein receptor gene duplicates exons, thereby, inactivating the gene product, leading to hypercholesterolemia.
187 citations
TL;DR: In this paper, the N-terminal activation domain of p53 was found to be sufficient for repressing Alu transcription in vitro, and mutation of positions 22 and 23 in this region impairs p53-mediated repression of an Alu template both in vitro and in vivo but has no effect on in vitro transcription of genes encoding 5S RNA, 7SL RNA, adenovirus VAI RNA, and tRNA.
Abstract: Wild-type p53 represses Alu template activity in vitro and in vivo. However, upstream activating sequence elements from both the 7SL RNA gene and an Alu source gene relieve p53-mediated repression. p53 also represses the template activity of the U6 RNA gene both in vitro and in vivo but has no effect on in vitro transcription of genes encoding 5S RNA, 7SL RNA, adenovirus VAI RNA, and tRNA. The N-terminal activation domain of p53, which binds TATA-binding protein (TBP), is sufficient for repressing Alu transcription in vitro, and mutation of positions 22 and 23 in this region impairs p53-mediated repression of an Alu template both in vitro and in vivo. p53's N-terminal domain binds TFIIIB, presumably through its known interaction with TBP, and mutation of positions 22 and 23 interferes with TFIIIB binding. These results extend p53's transcriptional role to RNA polymerase III-directed templates and identify an additional level of Alu transcriptional regulation.
114 citations
TL;DR: It is demonstrated that an ancestral Alu source sequence fortuitously acquired positive transcriptional control elements by insertion into the EPL locus, thereby providing biochemical evidence for a model which explains the selective amplification of Alu subfamilies.
Abstract: An Alu source gene, called the EPL Alu, was previously isolated by a phylogenetic strategy. Sequences flanking the EPL Alu family member stimulate its RNA polymerase III (Pol III) template activity in vitro. One cis-acting element maps within a 40-nucleotide region immediately upstream to the EPL Alu. This same region contains an Apt site which, when mutated, abolishes the transcriptional stimulation provided by this region. The flanking sequence, as assayed by gel mobility shift, forms sequence-specific complexes with several nuclear factors including Apt. These results demonstrate that an ancestral Alu source sequence fortuitously acquired positive transcriptional control elements by insertion into the EPL locus, thereby providing biochemical evidence for a model which explains the selective amplification of Alu subfamilies.
47 citations