Sökning: L773:0092 8674 OR L773:1097 4172
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Survival of DNA dam...
Survival of DNA damage in yeast directly depends on increased dNTP levels allowed by relaxed feedback inhibition of ribonucleotide reductase.
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- Chabes, Andrei (författare)
- Umeå universitet,Institutionen för medicinsk kemi och biofysik
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Georgieva, Bilyana (författare)
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- Domkin, Vladimir (författare)
- Umeå universitet,Institutionen för medicinsk kemi och biofysik
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visa fler...
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Zhao, Xiaolan (författare)
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Rothstein, Rodney (författare)
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- Thelander, Lars (författare)
- Umeå universitet,Institutionen för medicinsk kemi och biofysik
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visa färre...
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(creator_code:org_t)
- 2003
- 2003
- Engelska.
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Ingår i: Cell. - 0092-8674 .- 1097-4172. ; 112:3, s. 391-401
- Relaterad länk:
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https://urn.kb.se/re...
Abstract
Ämnesord
Stäng
- 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.
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