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首页> 外文期刊>Journal of Molecular Biology >Interplay among replicative and specialized DNA Polymerases determines failure or success of translesion synthesis pathways
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Interplay among replicative and specialized DNA Polymerases determines failure or success of translesion synthesis pathways

机译：复制和专门的DNA聚合酶之间的相互作用决定了跨病变合成途径的失败或成功

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摘要

Living cells possess a panel of specialized DNA polymerases that deal with the large diversity of DNA lesions that occur in their genomes. How specialized DNA polymerases gain access to the replication intermediate in the vicinity of the lesion is unknown. Using a model system in which a single replication blocking lesion can be bypassed concurrently by two pathways that leave distinct molecular signatures, we analyzed the complex interplay among replicative and specialized DNA polymerases. The system involves a single N-2-acetylaminofluorene guanine adduct within the NarI frameshift hot spot that can be bypassed concurrently by Pol II or Pol V, yielding a -2 frameshift or an error-free bypass product, respectively. Reconstitution of the two pathways using purified DNA polymerases Pol III, Pol II and Pol V and a set of essential accessory factors was achieved under conditions that recapitulate the known in vivo requirements. With this approach, we have identified the key replication intermediates that are used preferentially by Pol II and Pol V, respectively. Using single-hit conditions, we show that the beta-clamp is critical by increasing the processivity of Pol II during elongation of the slipped -2 frameshift intermediate by one nucleotide which, surprisingly, is enough to support subsequent elongation by Pol III rather than degradation. Finally, the proofreading activity of the replicative polymerase prevents the formation of a Pol II-mediated -1 frameshift product. In conclusion, failure or success of TLS pathways appears to be the net result of a complex interplay among DNA polymerases and accessory factors. (c) 2007 Elsevier Ltd. All rights reserved.
机译：活细胞拥有一组专门的DNA聚合酶，可处理其基因组中发生的大量DNA损伤。尚不清楚特异的DNA聚合酶如何进入病变附近的复制中间体。使用一个模型系统，其中单个复制阻滞性病变可通过两条途径同时被绕过，从而留下独特的分子特征，我们分析了复制性和专门性DNA聚合酶之间的复杂相互作用。该系统涉及NarI移码热点内的单个N-2-乙酰氨基芴鸟嘌呤加合物，可同时被Pol II或Pol V旁路，从而分别产生-2移码或无错旁路产物。在概括已知的体内需求的条件下，使用纯化的DNA聚合酶Pol III，Pol II和Pol V重建了两种途径。通过这种方法，我们已经确定了分别由Pol II和Pol V优先使用的关键复制中间体。使用单一命中条件，我们表明，β-钳制是至关重要的，它通过在滑动的-2移码中间体延长一个核苷酸的过程中增加Pol II的生产力，这令人惊讶地足以支持随后的Pol III延长而不是降解。最后，复制性聚合酶的校对活性可防止Pol II介导的-1移码产物的形成。总之，TLS途径的失败或成功似乎是DNA聚合酶和辅助因子之间复杂相互作用的最终结果。 （c）2007 Elsevier Ltd.保留所有权利。

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