Endogenous lesions, S-phase-independent spontaneous mutations, and evolutionary strategies for base excision repair
Endogenous lesions, S-phase-independent spontaneous mutations, and evolutionary strategies for base excision repair
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DOI：
10.1016/s0027-5107(98)00051-7
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发表时间：
1998-05-25
影响因子：
2.3
通讯作者：
Holmquist, GP
中科院分区：
文献类型：
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作者：
Holmquist, GP
我们从已发表的内源性基底病变水平计算出，我们的细胞在基底切除修复（BER）期间不断产生和切除，每天约有一百万个病变。修复糖基化酶也可以非特异性地切除额外数量的未受损的碱基。由此产生的无碱基位点每天由BER修复。聚合酶β的保真度为2.4 × 10 ~（-5），必须假设BER复合物中有额外的保真度机制来解释静息细胞的低突变率。组成性增加糖基化酶活性以防止内源性病变进入S期并变成突变的任何策略也将用于增加每天由正常未受损碱基的非特异性切除引起的突变数量。减少内源性损伤诱导突变的最佳盈亏平衡策略显然不是一种积极的修复，从噬菌体到真菌的低等生物都采用了每次细胞分裂产生0.0033个相应突变的策略，策略如下调S期外的糖基化酶活性以降低时间依赖性突变频率，同时留下损伤复制-诱发突变频率不变进行了讨论。(C)1998 Elsevier Science B. V.保留所有权利。
We calculate from published levels of endogenous base lesions that our cells constantly generate and excise during base excision repair (BER) about one million lesions per day. Repair glycosylases may also non-specifically excise an additional number of undamaged bases. The resulting abasic sites are repaired daily by BER. The fidelity of polymerase-beta is 2.4 X 10(-5) and one must postulate additional fidelity mechanisms in the BER complex to explain the low mutation rate of resting cells. Any strategy which constitutively increases glycosylase activity to prevent endogenous lesions from entering S-phase and becoming mutations will also serve to increase the number of mutations per day caused by non-specific excision of normal undamaged bases. The best break-even strategy for reducing endogenous lesion-induced mutations is clearly not one of avid repair, Lower organisms from bacteriophage to fungi have adopted strategies to generate 0.0033 consequential mutations per cell division, no more and no less. Strategies such as down regulating glycosylase activity outside of S-phase to reduce time-dependent mutation frequency while leaving lesion replication-induced mutation frequency unchanged are discussed. (C) 1998 Elsevier Science B.V. All rights reserved.