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| Patrick Cramer - | |
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RNA polymerase II is the central enzyme that synthesizes all eukaryotic
mRNA. Pol II is the endpoint of signalling pathways and its regulation
by many proteins underlies cell growth and differentiation. Structures
of the ten-subunit core of yeast RNA polymerase II (Pol II) in free
form (1, 2), in complex with DNA and RNA (3), and in complex with
alpha-amanitin (4) have elucidated the mRNA transcription mechanism
(reviewed in 5, 6). Based on this work models for the complete
12-subunit Pol II were obtained last year (7, 8). We have subsequently
solved the first structure of Pol II in complex with a transcription
factor, the elongation factor TFIIS, which can convert the enzyme into
a nuclease, to rescue arrested polymerases (9, 10). During this work,
we have determined structures of up to 550 kDa in molecular weight and
comprising 13 polypeptides and 3 strands of nucleic acids. I will first
summarize this work in light of both the technical and the biological
advances. I will then present unpublished structural and functional
data that provide insights into the coupling of transcription to mRNA
processing and into Pol II recycling (11, 12).
1. Cramer et al. Science 288, 640 (2000).
2. Cramer, Bushnell, Kornberg. Science 292, 1863 (2001).
3. Gnatt, Cramer, Fu, Bushnell, Kornberg. Science 292, 1876 (2001).
4. Bushnell, Cramer, Kornberg. PNAS 99, 1218 (2002).
5. Cramer. Curr. Op. Struct. Biol. 12, 89 (2002).
6. Cramer. Bioessays 24, 724 (2002).
7. Armache, Kettenberger, Cramer. PNAS 100, 6964 (2003).
8. Bushnell, Kornberg. PNAS 100, 6969 (2003).
9. Kettenberger, Armache, Cramer. Cell 114, 347 (2003).
10. Cramer. Curr. Op. Genet. Dev. 14, 218 (2004).
11. Meinhart, Cramer. Nature, in press (2004).
12. Kamenski, Heilmeier, Meinhart, Cramer, Mol. Cell, in press (2004).
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