TITLE

Structural basis for transcription elongation

STAFF

Cecilia Bartolucci
Alberto Cassetta
Doriano Lamba
Luciano Cellai*
Giuseppina Andreano*
Annalisa Masi*
[*] not in permanent position

CNR MODULE

PM.P06.001.001 Cristallography of Biomolecules and Functional Studies

KEYWORDS

RNA polymerase, Elongation complex, DNA-damage, Structural Biology

COLLABORATIONS

DESCRIPTION

DNA transcription by DNA-dependent RNA polymerases (RNAP) can be divided into three stages: initiation, elongation and termination. Elongation is highly processive, its different steps between synthesis, halting, substrate loading and RNA release depending on the interactions between RNAP, the nucleic acids signals and auxiliary transcription factors within the elongation complex (EC).
Structural details obtained by X-Ray crystallography would provide insights crucial for understanding the mechanistic aspects of transcription elongation and its processivity, fidelity and regulation, which in turn could have important medical applications by facilitating the design of novel antibiotics and anti-cancer drugs.
The elucidation of the complex between bacterial core RNAP and a DNA strand simulating a transcription bubble, coupled with an RNA strand of appropriate length is still lacking and would be of great importance for understanding the principles of transcription. In fact the core RNAP responsible for elongation, is highly homologous in prokaryote and eukaryotes and structural data obtained on either system would be of general interest
Structural details obtained from the resolution of X-Ray structures of cocrystals of DNA containing lesions and polymerases could help gain further insights into DNA repair and mutagenesis pathways. Considering the wide range of DNA damages and their specific recognition by different polymerases, a systematic structural study with stable analogues of DNA lesions would be of great interest.

[1] Cramer P. Multisuibunit RNA polymerases. Curr. Opin. Struct. Biol. 12, 89-97, 2002.
[2] Cramer P., Bushnell D. A., Kronberg R. D. Structural basis of transcription : RNA polymerase II at 2.8 A resolution Science, 298, 1387-1395, 2001.
[3] Korzheva N. et al. A structural model of transcription elongation. Science, 289, 619-625, 2000.

Elongation complex with an open transcription bubble, modeled on the crystal structure of the Taq core polymerase. Different subunits of the enzyme are shown in different colors. The DNA template strand is gold; the nontemplate strand green and the RNA transcript violett.

CONTACTS