Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Science 28 July 2006:
Vol. 313. no. 5786, pp. 518 - 520
DOI: 10.1126/science.1127422
Prev | Table of Contents | Next

Reports

Transcript-Assisted Transcriptional Proofreading

Nikolay Zenkin,1* Yulia Yuzenkova,1 Konstantin Severinov1,2,3*

Fidelity of template-dependent nucleic acid synthesis is the main determinant of stable heredity and error-free gene expression. The mechanism (or mechanisms) ensuring fidelity of transcription by DNA-dependent RNA polymerases (RNAPs) is not fully understood. Here, we show that the 3' end–proximal nucleotide of the nascent transcript stimulates hydrolysis of the penultimate phosphodiester bond by providing active groups and coordination bonds to the RNAP active center. This stimulation is much higher in the case of misincorporated nucleotide. We show that during transcription elongation, the hydrolytic reaction stimulated by misincorporated nucleotides proofreads most of the misincorporation events and thus serves as an intrinsic mechanism of transcription fidelity.

1 Waksman Institute, Rutgers University, Piscataway, NJ 08854, USA.
2 Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, NJ 08854, USA.
3 Institute of Molecular Genetics, Russian Academy of Sciences, Moscow, 123182 Russia.

* To whom correspondence should be addressed at Waksman Institute, 190 Frelinghuysen Road, Piscataway, NJ 08854, USA. E-mail: nicserzen{at}mail.ru (N.Z.); severik{at}waksman.rutgers.edu (K.S.)

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Structural Basis of Transcription: Backtracked RNA Polymerase II at 3.4 Angstrom Resolution.
D. Wang, D. A. Bushnell, X. Huang, K. D. Westover, M. Levitt, and R. D. Kornberg (2009)
Science 324, 1203-1206
   Abstract »    Full Text »    PDF »
Maintenance of RNA-DNA Hybrid Length in Bacterial RNA Polymerases.
T. Kent, E. Kashkina, M. Anikin, and D. Temiakov (2009)
J. Biol. Chem. 284, 13497-13504
   Abstract »    Full Text »    PDF »
Analysis of Promoter Targets for Escherichia coli Transcription Elongation Factor GreA In Vivo and In Vitro.
E. Stepanova, J. Lee, M. Ozerova, E. Semenova, K. Datsenko, B. L. Wanner, K. Severinov, and S. Borukhov (2007)
J. Bacteriol. 189, 8772-8785
   Abstract »    Full Text »    PDF »
Nonrandom variations in human cancer ESTs indicate that mRNA heterogeneity increases during carcinogenesis.
M. Brulliard, D. Lorphelin, O. Collignon, W. Lorphelin, B. Thouvenot, E. Gothie, S. Jacquenet, V. Ogier, O. Roitel, J.-M. Monnez, et al. (2007)
PNAS 104, 7522-7527
   Abstract »    Full Text »    PDF »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)