Abstract

One of the most common DNA lesions is the appearance of apurinic/apyrimidinic (AP-) sites. The main repair pathway for AP sites is initiated by apurinic/apyrimidinic endonuclease 1 (APE1). Upon hydrolysis of the phosphodiester bond by this enzyme, a one nucleotide gap flanked by 3′-hydroxyl and 5′‑deoxyribose phosphate groups on the 5′-side of the AP site is formed. After hydrolysis of the AP site, APE1 remains associated with the product for some time. In the present work, the ability of APE1 to form a product of covalent attachment of APE1 to DNA containing a gap with a 5′-deoxyribose phosphate residue was demonstrated. In addition, it was found that while in a complex with the product of hydrolysis of the AP site, APE1 exhibits 5'‑deoxyribose phosphate lyase activity, cleaving off the 5′-deoxyribose phosphate residue. The presence of lyase activity in APE1 may be important for the repair of AP sites if there is a deficiency of, or mutations in DNA polymerase β, the main enzyme that removes the 5′-deoxyribose phosphate group.

中文翻译：

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紫杉醇/嘧啶核糖核酸内切酶1的5'-脱氧核糖磷酸裂解酶活性

摘要

最常见的DNA损伤之一是嘌呤/嘧啶（AP-）位点的出现。AP位点的主要修复途径是由嘌呤/嘧啶内切核酸酶1（APE1）启动的。磷酸二酯键被该酶水解后，在AP位点5'侧形成一个侧翼为3'-羟基和5'-脱氧核糖磷酸基团的核苷酸缺口。AP位点水解后，APE1与产物保持一定的结合时间。在目前的工作中，证明了APE1形成APE1与包含具有5'-脱氧核糖磷酸残基的缺口的DNA共价连接的产物的能力。另外，发现与PE位点水解产物形成复合物时，APE1表现出5'-脱氧核糖磷酸裂解酶活性，切割出5'-脱氧核糖磷酸残基。