Survival of DNA damage in yeast directly depends on increased dNTP levels allowed by relaxed feedback inhibition of ribonucleotide reductase

Chabes, A., Georgieva, B., Domkin, V., Zhao, X. L., Rothstein, R., Thelander, L. (February 2003) Survival of DNA damage in yeast directly depends on increased dNTP levels allowed by relaxed feedback inhibition of ribonucleotide reductase. Cell, 112 (3). pp. 391-401. ISSN 0092-8674

URL: http://www.ncbi.nlm.nih.gov/pubmed/12581528
DOI: 10.1016/S0092-8674(03)00075-8

Abstract

In eukaryotes, DNA damage elicits a multifaceted response that includes cell cycle arrest, transcriptional activation of DNA repair genes, and, in multicellular organisms, apoptosis. We demonstrate that in Saccharomyces cerevisiae, DNA damage leads to a 6- to 8-fold increase in dNTP levels. This increase is conferred by an unusual, relaxed dATP feedback inhibition of ribonucleotide reductase (RNR). Complete elimination of dATP feedback inhibition by mutation of the allosteric activity site in RNR results in 1.6-2 times higher dNTP pools under normal growth conditions, and the pools increase an additional 11- to 17-fold during DNA damage. The increase in dNTP pools dramatically improves survival following DNA damage, but at the same time leads to higher mutation rates' We propose that increased survival and mutation rates result from more efficient translesion DNA synthesis at elevated dNTP concentrations.

Item Type: Paper
Uncontrolled Keywords: CELL-CYCLE SACCHAROMYCES-CEREVISIAE ALLOSTERIC REGULATION CHECKPOINT PATHWAYS MUTATOR PHENOTYPES ESCHERICHIA-COLI POLYMERASE-ETA SMALL-SUBUNIT CALF THYMUS IN-VITRO
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > DNA expression
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification
bioinformatics > genomics and proteomics > genetics & nucleic acid processing
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > dNTP
organism description > yeast
CSHL Authors:
Depositing User: Matt Covey
Date: February 2003
Date Deposited: 01 Jul 2013 20:26
Last Modified: 01 Jul 2013 20:26
Related URLs:
URI: http://repository.cshl.edu/id/eprint/27884

Actions (login required)

Administrator's edit/view item Administrator's edit/view item
CSHL HomeAbout CSHLResearchEducationNews & FeaturesCampus & Public EventsCareersGiving