The FHA domain of aprataxin interacts with the C-terminal region of XRCC1

The FHA domain of aprataxin interacts with the C-terminal region of XRCC1
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DOI:
10.1016/j.bbrc.2004.10.162
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发表时间:
2004-12-24
影响因子:
3.1
通讯作者:
Onodera, O
Onodera, O
中科院分区:
生物学4区
文献类型:
--
作者:
Date, H;Igarashi, S;Onodera, O

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Aprataxin(APTX)是早发性共济失调伴眼运动性失用症和低白蛋白血症(EAOH/AOA 1)的致病基因产物。在我们之前的研究中,我们发现APTX与X射线修复交叉互补组1(XRCC 1)相互作用,XRCC 1是一种在单链DNA断裂修复(SSBR)中发挥重要作用的支架蛋白。为了进一步表征APTX的功能,我们确定了相互作用所需的APTX和XRCC 1的结构域。我们证明了APTX的FHA结构域的20个N-末端氨基酸对于其与XRCC 1的C-末端区域(残基492-574)的相互作用是重要的。此外,我们发现聚(ADP-核糖)聚合酶-1(PARP-1)也与APTX免疫共沉淀。这些发现表明APTX与XRCC 1和PARP-1一起在SSBR中起重要作用。(C)2004年爱思唯尔公司All rights reserved.
Aprataxin (APTX) is the causative gene product for early-onset ataxia with ocular motor apraxia and hypoalbuminemia (EAOH/AOA1). In our previous study, we found that APTX interacts with X-ray repair cross-complementing group 1 (XRCC1), a scaffold protein with an essential role in single-strand DNA break repair (SSBR). To further characterize the functions of APTX, we determined the domains of APTX and XRCC1 required for the interaction. We demonstrated that the 20 N-terminal amino acids of the FHA domain of APTX are important for its interaction with the C-terminal region (residues 492-574) of XRCC1. Moreover, we found that poly (ADP-ribose) polymerase-1 (PARP-1) is also co-immunoprecipitated with APTX. These findings suggest that APTX, together with XRCC1 and PARP-1, plays an essential role in SSBR. (C) 2004 Elsevier Inc. All rights reserved.