- DNA Repair Mechanisms
- Virus-based gene therapy research
- Genomics and Chromatin Dynamics
- DNA and Nucleic Acid Chemistry
- CRISPR and Genetic Engineering
- Polyomavirus and related diseases
- Bacteriophages and microbial interactions
- Chromosomal and Genetic Variations
- RNA Research and Splicing
- Molecular Biology Techniques and Applications
- Animal Virus Infections Studies
- Animal Disease Management and Epidemiology
- Epigenetics and DNA Methylation
- RNA and protein synthesis mechanisms
- Microtubule and mitosis dynamics
- Cervical Cancer and HPV Research
- T-cell and Retrovirus Studies
- Cancer-related Molecular Pathways
- Vector-Borne Animal Diseases
- Plant Virus Research Studies
- Bacterial Genetics and Biotechnology
- Herpesvirus Infections and Treatments
- Animal Genetics and Reproduction
- RNA Interference and Gene Delivery
- Evolution and Genetic Dynamics
University of California, Berkeley
2011-2022
QB3
2011-2012
University of Alabama at Birmingham
2003
Cold Spring Harbor Laboratory
1974-2001
Istituto Pasteur
1998
University of Virginia
1997
Stanford University
1994
National Cancer Institute
1992
Lawrence Berkeley National Laboratory
1992
Institut Pasteur
1985
The fly Drosophila melanogaster is one of the most intensively studied organisms in biology and serves as a model system for investigation many developmental cellular processes common to higher eukaryotes, including humans. We have determined nucleotide sequence nearly all ∼120-megabase euchromatic portion genome using whole-genome shotgun sequencing strategy supported by extensive clone-based high-quality bacterial artificial chromosome physical map. Efforts are under way close remaining...
The protein Cdc45 plays a critical but poorly understood role in the initiation and elongation stages of eukaryotic DNA replication. To study Cdc45's function replication, we purified from Drosophila embryo extracts by combination traditional immunoaffinity chromatography steps found that exists stable, high-molecular-weight complex with Mcm2-7 hexamer GINS tetramer. Cdc45/Mcm2-7/GINS is associated an active ATP-dependent helicase function. RNA interference knock-down experiments targeting...
The mechanism by which transcription factors stimulate DNA replication in eukaryotes is unknown. Bovine papillomavirus synthesis requires the products of viral E1 gene and transcriptional activator protein encoded E2 gene. Experimental data showed that 68-kilodalton (kD) formed a complex with 48-kD factor. This bound specifically to origin replication, contains multiple binding sites for E2. Repressor proteins open reading frame failed suggesting 162-amino acid region participates...
The earliest stages of development in most metazoans are driven by maternally deposited proteins and mRNAs, with widespread transcriptional activation the zygotic genome occurring hours after fertilization, at a period known as maternal-to-zygotic transition (MZT). In Drosophila, MZT is preceded transcription small number genes that initiate sex determination, patterning, other early developmental processes; zinc-finger protein Zelda (ZLD) plays key role their activation. To better...
The lacI gene of Escherichia coli was used to score mutation in mammalian cells simian virus 40-based recombinant DNA vectors that provide for replication and selection both bacterial cells. Plasmid introduced into COS7 by DEAE-dextran transfection, allowed replicate the cells, then returned E. analysis. Mutants were observed at frequencies one several percent, compared with a spontaneous rate less than 10(-5). lesions include large number base substitutions, addition deletions,...
The Drosophila Myb complex has roles in both activating and repressing developmentally regulated DNA replication. To further understand biochemically the functions of complex, we fractionated embryo extracts relying upon affinity chromatography. We found that E2F2, DP, RBF1, RBF2, homolog LIN-52, a class B synthetic multivulva (synMuv) protein, copurify with components to form Myb-MuvB complex. In addition, transcriptional repressor lethal (3) malignant brain tumor L(3)MBT, histone...
We have demonstrated that the retinoblastoma gene product (Rb) can positively regulate transcription from fourth promoter of insulinlike growth factor II gene. Two copies a motif (the control element) similar to found in human c-fos, transforming beta 1, and c-myc promoters are responsible for conferring Rb regulation shown Sp1 bind stimulate element motif. Moreover, by using GAL4-Sp1 fusion protein, we directly regulates transcriptional activity vivo. These results indicate function as...
For efficient DNA replication of papillomaviruses, only two viral-encoded proteins, E1 and E2, are required. Other proteins factors provided by the host cell. E2 is an enhancer both transcription known to help bind cooperatively origin replication. sufficient for in extracts prepared from permissive cells, but activity enhanced E2. Here we show that purified can act as ATP-dependent helicase. To measure this activity, have used strand displacement, unwinding topologically constrained DNA,...
Rodent cells in culture which do not support SV40 replication can be stably transformed by the virus. The resulting cells, invariably harbor integrated viral DNA sequences (Sambrook et al. 1968; Hirai 1971; Gelb 1971), often manipulated to become infectious centers of production fusion with permissive simian (Gerber 1966; Watkins and Dulbecco 1967; Koprowski 1967). source progeny molecules is copy (see Discussion). This remarkable view fact that previous work from our laboratory others has...
The DNA context of nucleotides that a protein recognizes can influence the strength protein-DNA interaction. Moreover, in prokaryotes, understanding quantitative differences binding affinities result part from is often important describing regulatory mechanisms. Nevertheless, these issues have not been major focus yet for investigation interactions eukaryotes. In this study, we explored specificity and range BPV-1 E2 transcriptional activator has DNA. Because sites are positioned near...
Bovine papilloma virus (BPV) contains a cis-acting DNA element which can enhance transcription of distal promoters. Utilizing both direct and indirect transient transfection assays, we showed that 59-base-pair sequence from the BPV genome could activate simian 40 promoter distances exceeding 2.5 kilobases in an orientation-independent manner. In contrast to 5'-proximal localization other known viral activators, this was located immediately 3' early polyadenylation signal genome. Deletion...