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人类apurinic/apyrimidinic内核酶在3'错配的DNA上的外核分解活性

Kai-Ming Chou¹, Yung-Chi Cheng

¹Department of Pharmacology, Yale University School of Medicine, New Haven, CT 06520, USA.

|February 8, 2002

概括

人类apurinic/apyrimidinic内核酶 (APE1) 对于DNA修复至关重要. 这项研究揭示了APE1.

科学领域:

分子生物学分子生物学
遗传学是一个遗传学.
生物化学生物化学

背景情况:

人类apurinic/apyrimidinic内核酶 (APE1) 对于DNA基切除修复 (BER) 是至关重要的.
APE1将DNA骨干5'切割到基底部部位,从而促进DNA聚合酶β介导的修复.
在小鼠中失去APE1同类物导致早期胚胎致死性,强调其至关重要的作用.

研究的目的:

调查APE1的新功能,超出其在BER中的正规作用.
为了描述APE1在不匹配的DNA末端上的外核酶活性.
评估APE1外核酶活性对DNA修复忠实性和抗病毒药物疗效的影响.

主要方法:

在实验室中复制基础切除修复系统.
酶分析检测和量化APE1在不匹配DNA上的外核酶活性.
在存在或缺少APE1.1的情况下分析DNA修复动力学.

主要成果:

APE1在破裂或缺口DNA中的3'不匹配的脱氧核糖核酸上表现出DNA外核酶活性.
这种外核酶活动的效率与DNA间隙大小相反.
在体外,APE1的存在对于被切断的不匹配DNA的有效重聚至关重要.
APE1可以从DNA中去除特定的抗HIV核酸类型 (例如,AZT,ddT).

结论:

APE1具有一种新的3'外核酶活性,可以提高DNA修复效率.
这种活动可能代表了对不匹配的DNA修复机制的新机制.
APE1的外核酶功能可能会影响某些抗病毒核酸类型的治疗指数.

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