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Probing the Thermodynamics of Incorporation of N6‐methyl‐dATP Opposite an Abasic Site, dCMP, and dTMP During Simulated DNA Synthesis by Differential Scanning Calorimetry
ChemistrySelect ( IF 2.1 ) Pub Date : 2018-12-07 , DOI: 10.1002/slct.201803565
Jaroslav Malina 1 , Viktor Brabec 1
Affiliation  

Previous reports indicated that when an abasic (apurinic/apyrimidinic, AP) site is bypassed by DNA polymerases, dATP is preferentially inserted. Here we evaluate, using differential scanning calorimetry, the thermodynamic changes associated with incorporation of N6‐methyl‐dATP opposite an AP site, dCMP, and dTMP during simulated DNA polymerization. The results confirm that AP sites block DNA polymerases one nucleotide prior to the lesion. Thermodynamic data imply that the propensity of N6‐methyl‐dAMP for elongation, when incorporated opposite an AP site, is higher than that of dAMP in agreement with a higher promutagenic potential of N6‐methyl‐dATP if placed opposite a non‐instructional DNA lesion, such as an AP site.

中文翻译:

通过差示扫描量热法研究模拟碱基合成中与碱基位点,dCMP和dTMP相反的N6-甲基-dATP掺入的热力学

先前的报道表明,当无碱基(apurinic / apyrimidinic,AP)位点被DNA聚合酶绕过时,dATP会被优先插入。在这里,我们使用差示扫描量热法评估了在模拟DNA聚合过程中与AP位置相对的N 6-甲基-dATP,dCMP和dTMP掺入的热力学变化。结果证实,AP位点在损伤之前阻断了一个核苷酸的DNA聚合酶。热力学数据暗示的倾向Ñ 6 -甲基-湿伸长率,当AP位点相对并入,比在与协议的较高promutagenic潜在潮湿的更高Ñ 6 -甲基-如果的dATP相对放置的非指导DNA损伤,例如AP位点。
更新日期:2018-12-07
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