Nonspecific DNA binding and coordination of the first two steps of base excision repair.
Nonspecific DNA binding and coordination of the first two steps of base excision repair.
复制标题
DOI：
10.1021/bi100889r
复制
发表时间：
2010-09-14
期刊：
影响因子：
2.9
通讯作者：
O'Brien, Patrick J.
中科院分区：
文献类型：
--
作者：
Baldwin, Michael R.;O'Brien, Patrick J.
碱基切除修复 (BER) 途径可修复 DNA 中多种受损的核碱基。该途径由 DNA 修复糖基化酶启动，该酶定位损伤位点并催化受损核碱基的切除。所得脱碱基位点由无嘌呤/无嘧啶位点核酸内切酶 1 (APE1) 进一步加工，以创建带有 3'-羟基的单链切口，作为 DNA 修复合成的引物。由于脱碱基位点具有高度诱变性，因此协调 BER 途径的步骤至关重要。大多数人类糖基化酶与其脱碱基产物紧密结合。 APE1 取代了结合的糖基化酶，从而刺激多次转换碱基切除。有人提出，APE1 的刺激涉及直接的蛋白质-蛋白质相互作用，但在 APE1 刺激的糖基化酶中尚未发现共同的相互作用基序。我们使用各种对称和不对称的含有损伤的寡核苷酸来表征 APE1 对烷基腺嘌呤 DNA 糖基化酶 (AAG) 的刺激。对多种底物的有效刺激有利于 AAG 和 APE1 可以同时与 DNA 结合但可能不直接相互作用的模型。相反，AAG 和 APE1 两者的非特异性 DNA 结合使 APE1 能够取代 AAG 的脱碱基位点。 AAG 不会转移到溶液中，而是仍与相邻的未损坏位点结合。我们提出非特异性 DNA 结合相互作用允许脱碱基位点短暂暴露，以便它可以被 APE1 捕获。
The base excision repair (BER) pathway repairs a wide variety of damaged nucleobases in DNA. This pathway is initiated by a DNA repair glycosylase, which locates the site of damage and catalyzes the excision of the damaged nucleobase. The resulting abasic site is further processed by apurinic/apyrimidinic site endonuclease 1 (APE1) to create a single strand nick with the 3'-hydroxyl that serves as a primer for DNA repair synthesis. Since an abasic site is highly mutagenic it is critical that the steps of the BER pathway be coordinated. Most human glycosylases bind tightly to their abasic product. APE1 displaces the bound glycosylase, thereby stimulating multiple turnover base excision. It has been proposed that direct protein-protein interactions are involved in the stimulation by APE1, but no common interaction motifs have been identified among the glycosylases that are stimulated by APE1. We characterized the APE1 stimulation of alkyladenine DNA glycosylase (AAG) using a variety of symmetric and asymmetric lesion-containing oligonucleotides. Efficient stimulation on a wide variety of substrates favors a model whereby both AAG and APE1 can simultaneously bind to DNA, but may not interact directly. Rather, nonspecific DNA binding by both AAG and APE1 enables APE1 to replace AAG at the abasic site. AAG is not displaced into solution, but remains bound to an adjacent undamaged site. We propose that nonspecific DNA binding interactions allow transient exposure of the abasic site so that it can be captured by APE1.
登录
查看更多内容
影响因子：
2.9
作者：
Carey, DC;Strauss, PR
通讯作者：
Strauss, PR
影响因子：
4.8
作者：
Katafuchi, A;Nakano, T;Ide, H
通讯作者：
Ide, H
影响因子：
4.8
作者：
Fitzgerald, Megan E.;Drohat, Alexander C.
通讯作者：
Drohat, Alexander C.
影响因子：
2.9
作者：
OHANDLEY, S;SCHOLES, CP;CUNNINGHAM, RP
通讯作者：
CUNNINGHAM, RP
影响因子：
2.9
作者：
BOORSTEIN, RJ;HILBERT, TP;TEEBOR, GW
通讯作者：
TEEBOR, GW