Evidence for lesion bypass by yeast replicative DNA polymerases during DNA damage.
Evidence for lesion bypass by yeast replicative DNA polymerases during DNA damage.
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DOI：
10.1093/nar/gkn555
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发表时间：
2008-10
影响因子：
14.9
通讯作者：
Chabes A
中科院分区：
文献类型：
--
作者：
Sabouri N;Viberg J;Goyal DK;Johansson E;Chabes A
负责脱氧核糖核苷酸（dNTP）合成的核糖核苷酸还原酶在所有生物体中响应于DNA损伤而上调。在酿酒酵母中，dNTP浓度响应于DNA损伤而增加1.6至8倍。这种浓度增加与DNA损伤耐受性的改善有关，表明在升高的dNTP浓度下跨损伤DNA合成更有效。在这里，我们表明，在一个酵母菌株与所有专门translesion DNA聚合酶删除，4-硝基喹啉氧化物（4-NQO）处理增加突变频率约3倍，并在dNTP浓度的增加显着提高该菌株的耐受性4-NQO诱导的损害。在体外，在单次击中条件下，复制型DNA聚合酶ε在S期dNTP浓度下不绕过7，8-二氢-8-氧代鸟嘌呤损伤（8-oxoG，由4-NQO产生的损伤之一），但在DNA损伤状态dNTP浓度下以19-27%的效率绕过相同的损伤。与8-oxoG相对插入的核苷酸是dATP。我们认为，在S.酿酒酵母增加的dNTP浓度允许复制型DNA聚合酶绕过某些DNA损伤。
The enzyme ribonucleotide reductase, responsible for the synthesis of deoxyribonucleotides (dNTP), is upregulated in response to DNA damage in all organisms. In Saccharomyces cerevisiae, dNTP concentration increases ∼6- to 8-fold in response to DNA damage. This concentration increase is associated with improved tolerance of DNA damage, suggesting that translesion DNA synthesis is more efficient at elevated dNTP concentration. Here we show that in a yeast strain with all specialized translesion DNA polymerases deleted, 4-nitroquinoline oxide (4-NQO) treatment increases mutation frequency ∼3-fold, and that an increase in dNTP concentration significantly improves the tolerance of this strain to 4-NQO induced damage. In vitro, under single-hit conditions, the replicative DNA polymerase ε does not bypass 7,8-dihydro-8-oxoguanine lesion (8-oxoG, one of the lesions produced by 4-NQO) at S-phase dNTP concentration, but does bypass the same lesion with 19–27% efficiency at DNA-damage-state dNTP concentration. The nucleotide inserted opposite 8-oxoG is dATP. We propose that during DNA damage in S. cerevisiae increased dNTP concentration allows replicative DNA polymerases to bypass certain DNA lesions.
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DOI：
10.1016/s0006-291x(86)80036-5
发表时间：
1986-09-01
影响因子：
3.1
作者：
KOHDA, K;TADA, M;KAWAZOE, Y
通讯作者：
KAWAZOE, Y
影响因子：
10.5
作者：
ELLEDGE, SJ;DAVIS, RW
通讯作者：
DAVIS, RW
影响因子：
30.8
作者：
Haracska, L;Yu, SL;Prakash, S
通讯作者：
Prakash, S
影响因子：
3.8
作者：
Lis, Ewa T.;O'Neill, Bryan M.;Romesberg, Floyd E.
通讯作者：
Romesberg, Floyd E.
影响因子：
14.9
作者：
McCulloch, SD;Kokoska, RJ;Kunkel, TA
通讯作者：
Kunkel, TA