Genetic evidence for a link between glycolysis and DNA replication.
Genetic evidence for a link between glycolysis and DNA replication.
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DOI：
10.1371/journal.pone.0000447
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发表时间：
2007-05-16
期刊：
影响因子：
3.7
通讯作者：
Ehrlich SD
中科院分区：
文献类型：
--
作者：
Jannière L;Canceill D;Suski C;Kanga S;Dalmais B;Lestini R;Monnier AF;Chapuis J;Bolotin A;Titok M;Le Chatelier E;Ehrlich SD
生物学中一个具有挑战性的目标是了解主要细胞功能是如何整合的，以便细胞在广泛的营养条件下实现活力和最佳适应性。我们在这里报告糖酵解和DNA合成之间的紧密联系。在分析枯草芽孢杆菌中热敏复制突变体的抑制子时发现的这种联系非常强，因为某些代谢改变完全恢复了复制突变体的活力，否则在高温限制性温度下会发生DNA合成的致命停滞。通过这种改变完全恢复活力仅限于在三个延伸因子（滞后链DnaE聚合酶、引发酶和解旋酶）中具有突变的细胞，所述三个延伸因子来自大部分复制蛋白中受影响的热敏突变体。恢复活力的结果，至少部分地，从维持复制蛋白质的活性在高温下。生理学研究表明，这种恢复依赖于糖酵解/代谢途径的三碳部分的活性，并发生在糖酵解和代谢方案。在糖酵解的三碳部分的基因表达的一个狭窄范围内，恢复突然发生。然而，该范围的绝对值随所讨论的等位基因而变化很大。最后，细胞活力的恢复似乎不是生长速率降低或诱导主要应激反应的结果。我们的研究结果为DNA链延长与糖酵解的遗传系统提供了第一个证据。它的作用可能是调节DNA合成的某些方面，以响应环境提供的能量和潜在的机制进行了讨论。有人提出，相关系统是无处不在的。
A challenging goal in biology is to understand how the principal cellular functions are integrated so that cells achieve viability and optimal fitness in a wide range of nutritional conditions. We report here a tight link between glycolysis and DNA synthesis. The link, discovered during an analysis of suppressors of thermosensitive replication mutants in bacterium Bacillus subtilis, is very strong as some metabolic alterations fully restore viability to replication mutants in which a lethal arrest of DNA synthesis otherwise occurs at a high, restrictive, temperature. Full restoration of viability by such alterations was limited to cells with mutations in three elongation factors (the lagging strand DnaE polymerase, the primase and the helicase) out of a large set of thermosensitive mutants affected in most of the replication proteins. Restoration of viability resulted, at least in part, from maintenance of replication protein activity at high temperature. Physiological studies suggested that this restoration depended on the activity of the three-carbon part of the glycolysis/gluconeogenesis pathway and occurred in both glycolytic and gluconeogenic regimens. Restoration took place abruptly over a narrow range of expression of genes in the three-carbon part of glycolysis. However, the absolute value of this range varied greatly with the allele in question. Finally, restoration of cell viability did not appear to be the result of a decrease in growth rate or an induction of major stress responses. Our findings provide the first evidence for a genetic system that connects DNA chain elongation to glycolysis. Its role may be to modulate some aspect of DNA synthesis in response to the energy provided by the environment and the underlying mechanism is discussed. It is proposed that related systems are ubiquitous.
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影响因子：
4.8
作者：
Fitch, MJ;Donato, JJ;Tye, BK
通讯作者：
Tye, BK
影响因子：
4.8
作者：
Chang, VK;Fitch, MJ;Tye, BK
通讯作者：
Tye, BK
影响因子：
56.9
作者：
Dervyn, E;Suski, C;Ehrlich, SD
通讯作者：
Ehrlich, SD
DOI：
10.1073/pnas.082112499
发表时间：
2002-04-30
影响因子：
11.1
作者：
Canback, B;Andersson, SGE;Kurland, CG
通讯作者：
Kurland, CG
影响因子：
3.2
作者：
Blinkova, A;Hermandson, MJ;Walker, JR
通讯作者：
Walker, JR