Activation of Chromosomal DNA Replication in Saccharomyces cerevisiae by Acidic Transcriptional Activation Domains

Li, R., Yu, D. S., Tanaka, M., Zheng, L., Berger, S. L., Stillman, B. (March 1998) Activation of Chromosomal DNA Replication in Saccharomyces cerevisiae by Acidic Transcriptional Activation Domains. Molecular and Cellular Biology, 18 (3). pp. 1296-1302. ISSN 0270-7306



A large body of evidence from viral systems has established that transcription factors play an important and direct role in activating viral DNA replication. Among the transcriptional activation domains that can stimulate viral DNA replication are acidic domains such as those derived from herpes simplex virus VP16 and the tumor suppressor p53. Here we show that acidic activation domains can also activate a cellular origin of replication in a chromosomal context. When tethered to the yeast ARS1 (autonomously replicating sequence 1) origin of replication, both VP16 and p53 activation domains can enhance origin function. In addition, the C-terminal acidic region of the yeast transcription factor ABF1, which normally activates the ARS1 origin, is sufficient for activating ARS1 function when tethered to the origin. Mutations at residues Trp-53 and Phe-54 of a 20-residue (41 to 60) activation region of p53 abolish the activation of both replication and transcription, suggesting that the same structural determinants may be employed to activate both processes in yeast. Furthermore, using a two-dimensional gel electrophoresis method, we demonstrate that the GAL4-p53 chimeric activator can activate initiation of chromosomal replication from an origin inserted at the native ARS1 locus. These findings strongly suggest functional conservation of the mechanisms used by the acidic activation domains to activate viral DNA replication in mammalian cells and chromosomal replication in yeast.

Item Type: Paper
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > DNA replication
CSHL Authors:
Communities: CSHL labs > Stillman lab
Highlight: Stillman, Bruce W.
Depositing User: CSHL Librarian
Date: 1 March 1998
Date Deposited: 06 Mar 2012 15:01
Last Modified: 20 Jun 2017 19:30
PMCID: PMC108842
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