Specificity versus Processivity in the Sequential Modification of DNA: A Study of DNA Adenine Methyltransferase

Specificity versus Processivity in the Sequential Modification of DNA: A Study of DNA Adenine Methyltransferase
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DOI:
10.1021/acs.jpcb.7b10349
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发表时间:
2018-01-25
影响因子:
3.3
通讯作者:
Brown, Frank L. H.
Brown, Frank L. H.
中科院分区:
化学3区
文献类型:
--
作者:
Barel, Itay;Naughton, Brigitte;Brown, Frank L. H.

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对已发表的实验结果和新的实验结果进行了详细的分析,用于细菌DNA腺嘌呤甲基转移酶(Dam)催化的两个位点DNA底物(位点间隔在100和800 bp之间)的甲基化动力学。先前报道的第二次甲基化事件(相对于第一次甲基化)的速率增强被证明是由于单甲基化DNA的底物特异性高于未甲基化DNA的底物特异性,而不是同一拷贝的Dam对两个位点的进行性周转。一个基本的模型,建议干净地适合实验数据在很宽的范围内的站点间的分离。该模型假设在同一DNA链上的竞争性未甲基化Dam位点之间存在环介导的干扰。
A detailed analysis is carried out on both published experimental results and new experiments for the methylation kinetics of two site DNA substrates (with site separations between 100 and 800 bp) catalyzed by bacterial DNA adenine methyltransferase (Dam). A previously reported rate enhancement for the second methylation event (relative to that of the first methylation) is shown to result from elevated substrate specificity for singly methylated DNA over that of unmethylated DNA and not processive turnover of both sites by the same copy of Dam. An elementary model is suggested that cleanly fits the experimental data over a broad range of intersite separations. The model hypothesizes a looping mediated interference between competing unmethylated Dam sites on the same DNA strand.