Mutation in resting cells: the role of endogenous DNA damage.
Mutation in resting cells: the role of endogenous DNA damage.
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静息细胞突变：内源性 DNA 损伤的作用。
DOI：
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发表时间：
1996
期刊：
影响因子：
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通讯作者：
B. Bridges
中科院分区：
文献类型：
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作者：
B. Bridges
在大肠杆菌中，新的自发突变可能出现在不分裂的细菌中，其中几乎没有DNA合成。这些突变几乎都是那些使细胞恢复生长的突变，这种现象被称为定向突变或适应性突变。通过对DNA修复缺陷菌株的研究，越来越多的证据表明，内源性诱变剂造成的损害可能是此类突变的重要来源。可能错误编码的DNA损伤可以解释明显的适应行为，因为如果“突变”的RNA转录本提供足够的优势，细胞被触发进入循环状态，那么下一轮DNA复制将可能通过DNA错误编码事件修复突变。在这方面最重要的损伤似乎是8-oxoG，它可以与腺嘌呤或胞嘧啶配对，从而引起G到T的转换。在不生长的修复熟练细菌中，几乎一半的G到T转换都是由它引起的。烷基化作用有助于转换和颠换的产生，但只有A：T碱基对上的那些对修复熟练的细菌是重要的。也有报道称，一种病变对UvrA、B、C依赖的切除修复敏感，但它在具有切除修复的细菌中是否重要尚未得到解决。关于哺乳动物细胞的数据几乎不存在，但有证据表明，有丝分裂后神经元中可以发生活体的点突变。最近的数据表明，在不分裂的细菌中可能存在大量隐秘的DNA周转，这一潜在的假设受到了挑战，即在不分裂的细菌中几乎没有DNA合成。
In E coli, new spontaneous mutations can arise in bacteria that are non-dividing and in which there is little or no DNA synthesis. These mutations are almost invariably those that enable the cell to resume growth, a phenomenon that has been termed directed or adaptive mutation. Evidence is accumulating from studies with DNA repair deficient strains that damage produced by endogenous mutagens may be an important source of such mutations. A DNA lesion that can miscode can explain the apparent adaptive behaviour since if a "mutant" RNA transcript confers sufficient advantage that the cell is triggered into a cycling state, the ensuing round of DNA replication will be likely to fix the mutation by means of a DNA miscoding event. The most important lesion in this respect appears to be 8-oxoG, which can pair equally well with adenine or cytosine and so give rise to G to T transversions. It is responsible for almost half the G to T transversions arising in non-growing repair proficient bacteria. Alkylations contribute to the production of both transitions and transversions but only those at A:T base pairs are important in repair proficient bacteria. There is also a report of a lesion susceptible to UvrA,B,C dependent excision repair, but whether it is important in bacteria possessing excision repair has not been addressed. Data on mammalian cells are almost non-existent, but there is evidence that point mutations can occur in vivo in postmitotic neurons. The underlying assumption that there is little or no DNA synthesis in non-dividing bacteria has been challenged by recent data suggesting that there may be extensive cryptic DNA turnover.