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首页> 外文期刊>Biochemistry >Efficiency of extension of mismatched primer termini across from cisplatin and oxaliplatin adducts by human DNA polymerases beta and eta in vitro
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Efficiency of extension of mismatched primer termini across from cisplatin and oxaliplatin adducts by human DNA polymerases beta and eta in vitro

机译：人DNA聚合酶β和eta体外错配引物末端延伸至顺铂和奥沙利铂加合物的效率

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DNA polymerases beta and eta are among the few eukaryotic polymerases known to efficiently bypass cisplatin and oxaliplatin adducts in vitro.Our laboratory has previously established that both polymerases misincorporated dTTP with high frequency across from cisplatin-and oxaliplatin-GG adducts.This decrease in polymerase fidelity on platinum-damaged DNA could lead to in vivo mutations,it this base substitution were efficiently elongated.In this study,we performed a steady-state kinetic analysis of the steps required for fixation of dTTP misinsertion during translesion synthesis past cisplatin-and oxaliplatin-GG adductsby pol beta and pol eta.The efficiency of translesion synthesis by pol eta past Pt-GG adducts was very similar to that observed for this polymerase when the template contains thymine-thymine dimers.This finding suggested that pol eta could play a role in translesion synthesis past platinum-GG adducts in vivo.On the other hand,translesion synthesis past platinum-GG adducts by pol beta was much less efficient.Translesion synthesis by pol eta is likely to be predominantly error-free,since the probability of correct insertion and extension by pol eta was 1000-2000-fold greater than the probability of incorrect insertion and extension.Our results also indicated that for pol eta the frequency of misincorporation is the same across from the 3'G and the 5'G of the platinum-GG adducts for both cisplatin and oxaliplatin adducts.On the other hand,pol beta is more likely to misinsert at the 3'G of the adducts and misinsertion occurs at higher frequency for oxaliplatin-GG than for cisplatin-GG adducts.
机译：DNA聚合酶β和eta是已知在体外能有效绕过顺铂和奥沙利铂加合物的几种真核聚合酶之一。我们的实验室先前已经确定，这两种聚合酶都错配了dTTP，并在顺铂和奥沙利铂-GG加合物之间发生频率很高，从而降低了聚合酶保真度。铂损伤的DNA可能导致体内突变，这种碱基取代被有效地延长。在这项研究中，我们对通过顺铂和奥沙利铂-进行的损伤合成中固定dTTP插入错误所需的步骤进行了稳态动力学分析。通过pol beta和pol eta生成的GG加合物.pol eta超过Pt-GG加合物的跨病变合成效率与在模板中包含胸腺嘧啶-胸腺嘧啶二聚体时观察到的聚合酶效率非常相似。在体内通过铂-GG加合物进行跨病变合成。另一方面，通过铂-GG加合物进行跨病变合成pol Beta的效率低得多。pol eta的转运合成可能几乎没有错误，因为pol eta正确插入和延伸的可能性比错误插入和延伸的可能性大1000-2000倍。结果还表明，对于pol eta，顺铂和奥沙利铂加合物的3'G和5'G铂-GG加合物的错配频率相同。另一方面，polβ更有可能误插入在加合物的3'G处，奥沙利铂-GG的错误插入发生频率高于顺铂-GG加合物。

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