Identification and characterization of mitochondrial abasic (AP)-endonuclease in mammalian cells.
Identification and characterization of mitochondrial abasic (AP)-endonuclease in mammalian cells.
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DOI：
10.1093/nar/gkl177
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发表时间：
2006
影响因子：
14.9
通讯作者：
Mitra S
中科院分区：
文献类型：
--
作者：
Chattopadhyay R;Wiederhold L;Szczesny B;Boldogh I;Hazra TK;Izumi T;Mitra S
脱碱基核酸内切酶（AP-endonuclease，APE）负责AP位点的修复和单链DNA的3′端阻断基团的断裂，这些阻断基团是在细胞核和线粒体中通过DNA碱基切除修复（DNA base excision repair，BER）途径自发产生的或在损伤或异常碱基修复过程中产生的。哺乳动物细胞仅表达一种核APE，即36 kDa APE 1，这是生存所必需的。哺乳动物线粒体（mt）BER酶以外的mtAPE的特点。为了鉴定和表征mtAPE，我们从牛肝线粒体中纯化APE活性至接近同质，并表明mtAPE相对于APE 1具有3倍高的比活性，其源自APE 1，缺失了含有核定位信号的33个N-末端残基。mtAPE大小的产品可以通过孵育35 S标记的APE 1与粗线粒体提取物，但不与胞质或核提取物，这表明，由一个特定的线粒体相关的N-末端肽酶的APE 1裂解是线粒体输入的先决条件。mtAPE的低丰度，特别是在培养的细胞中，可能是其早期缺乏Western分析检测的原因。
Abasic (AP)-endonuclease (APE) is responsible for repair of AP sites, and single-strand DNA breaks with 3′ blocking groups that are generated either spontaneously or during repair of damaged or abnormal bases via the DNA base excision repair (BER) pathway in both nucleus and mitochondria. Mammalian cells express only one nuclear APE, 36 kDa APE1, which is essential for survival. Mammalian mitochondrial (mt) BER enzymes other than mtAPE have been characterized. In order to identify and characterize mtAPE, we purified the APE activity from beef liver mitochondria to near homogeneity, and showed that the mtAPE which has 3-fold higher specific activity relative to APE1 is derived from the latter with deletion of 33 N-terminal residues which contain the nuclear localization signal. The mtAPE-sized product could be generated by incubating 35S-labeled APE1 with crude mitochondrial extract, but not with cytosolic or nuclear extract, suggesting that cleavage of APE1 by a specific mitochondria-associated N-terminal peptidase is a prerequisite for mitochondrial import. The low abundance of mtAPE, particularly in cultured cells might be the reason for its earlier lack of detection by western analysis.
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影响因子：
3.3
作者：
Hudson, EK;Hogue, BA;Hansford, RG
通讯作者：
Hansford, RG
影响因子：
5.6
作者：
Frossi, B;Tell, G;Pucillo, C
通讯作者：
Pucillo, C
影响因子：
4.8
作者：
Karahalil, B;Hogue, BA;Bohr, VA
通讯作者：
Bohr, VA
影响因子：
2.9
作者：
DOMENA, JD;MOSBAUGH, DW
通讯作者：
MOSBAUGH, DW
DOI：
10.1073/pnas.0500986102
发表时间：
2005-04-19
影响因子：
11.1
作者：
Izumi, T;Brown, DB;Mitra, S
通讯作者：
Mitra, S