Stimulation of DNA replication in Saccharomyces cerevisiae by a glutamine- and proline-rich transcriptional activation domain.
Glutamine-rich Sp1 and proline-rich CTF1, two extensively studied mammalian transcription factors, bind to origins of replication in DNA tumor viruses and stimulate viral DNA replication in mammalian cells. Here it is shown that, when tethered to a plasmid-borne cellular origin of replication, the activation domains of both proteins can enhance origin function in Saccharomyces cerevisiae. Hydrophobic patches in Sp1 and CTF1 that mediate transcriptional activation in higher eukaryotes are also important for activation of replication in yeast. However, only the activation domain of CTF1 can enhance initiation of replication from a chromosomally embedded origin. This correlates with the ability of CTF1 to alter the local chromatin structure around the chromosomal origin of replication. The CTF1-induced chromatin remodeling occurs at multiple stages of the cell cycle. These findings strongly suggest a high degree of conservation in the mechanisms used by various types of transcription factors to stimulate viral and cellular DNA replication in eukaryotes.
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Department of Biochemistry, Health Sciences Center, University of Virginia, Charlottesville, Virginia 22908, USA. rlt2@virginia.edu
D000595:Amino Acid Sequence; D002843:Chromatin / Q000737:chemistry / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone; D015825:Chromosomes, Fungal; D004261:DNA Replication; D004271:DNA, Fungal / Q000096:biosynthesis*; D004268:DNA-Binding Proteins; D005656:Fungal Proteins / Q000737:chemistry / Q000378:metabolism; D005973:Glutamine / Q000378:metabolism*; D010957:Plasmids; D011392:Proline / Q000378:metabolism*; D011487:Protein Conformation; D018741:Replication Origin; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins; D016329:Sp1 Transcription Factor / Q000737:chemistry / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D015533:Transcriptional Activation
C066751:CHL1 protein, S cerevisiae; D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D004271:DNA, Fungal; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; C052130:GAL4 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D016329:Sp1 Transcription Factor; D014157:Transcription Factors; D005973:Glutamine; D011392:Proline