Stimulation of NEIL2-mediated oxidized base excision repair via YB-1 interaction during oxidative stress
Stimulation of NEIL2-mediated oxidized base excision repair via YB-1 interaction during oxidative stress
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DOI：
10.1074/jbc.m704672200
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发表时间：
2007-09-28
影响因子：
4.8
通讯作者：
Hazra, Tapas K.
中科院分区：
文献类型：
--
作者：
Das, Soumita;Chattopadhyay, Ranajoy;Hazra, Tapas K.
NEIL 2（Nei-like-2）是哺乳动物细胞中的四种氧化碱基特异性DNA糖基化酶（OGG 1、NTH 1、NEIL 1和NEIL 2）之一，其对双链DNA的碱基切除活性很差。为了测试一种或多种蛋白质在体内调节其活性的可能性，我们对NEIL 2免疫复合物进行了质谱分析，并将Y盒结合（YB-1）蛋白鉴定为NEIL 2的稳定相互作用伴侣。我们在这里表明，YB-1不仅与NEIL 2物理相互作用，但它也通过刺激其碱基切除活性的7倍，在功能上合作。此外，YB-1与其他NEIL 2相关的BER蛋白，即DNA连接酶III α和DNA聚合酶β相互作用，因此可以形成大的多蛋白复合物。YB-1，通常存在于细胞质中，在UVA诱导的氧化应激期间易位到细胞核，伴随着其与NEIL 2的增加的关联和激活。NEIL 2启动的碱基切除活性在YB-1耗尽的细胞中显著降低。因此，YB-1似乎在氧化应激下NEIL 2介导的修复中具有新的调节作用。
The recently characterized enzyme NEIL2 (Nei-like-2), one of the four oxidized base-specific DNA glycosylases (OGG1, NTH1, NEIL1, and NEIL2) in mammalian cells, has poor base excision activity from duplex DNA. To test the possibility that one or more proteins modulate its activity in vivo, we performed mass spectrometric analysis of the NEIL2 immunocomplex and identified Y box-binding (YB-1) protein as a stably interacting partner of NEIL2. We show here that YB-1 not only interacts physically with NEIL2, but it also cooperates functionally by stimulating its base excision activity by 7-fold. Moreover, YB-1 interacts with the other NEIL2-associated BER proteins, namely, DNA ligase III alpha and DNA polymerase beta and thus could form a large multiprotein complex. YB-1, normally present in the cytoplasm, translocates to the nucleus during UVA-induced oxidative stress, concomitant with its increased association with and activation of NEIL2. NEIL2-initiated base excision activity is significantly reduced in YB-1-depleted cells. YB-1 thus appears to have a novel regulatory role in NEIL2-mediated repair under oxidative stress.