Functional characterization of human MutY homolog (hMYH) missense mutation (R231L) that is linked with hMYH-associated polyposis
Functional characterization of human MutY homolog (hMYH) missense mutation (R231L) that is linked with hMYH-associated polyposis
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DOI：
10.1016/j.canlet.2006.09.016
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发表时间：
2007-05-18
期刊：
影响因子：
9.7
通讯作者：
Lu, A-Lien
中科院分区：
文献类型：
--
作者：
Bai, Haibo;Grist, Scott;Lu, A-Lien
MutY 同源物 (MYH) 可以在 DNA 复制过程中切除与鸟嘌呤或 7,8-二氢-8-氧代-鸟嘌呤 (8-oxoG) 相对的错误掺入的腺嘌呤；从而防止 G:C 到 T:A 颠换。人类 MYH 基因的种系突变与结直肠腺瘤性息肉病 (MAP) 的隐性遗传有关。在这里，我们表征了一种新发现的 MAP 相关 MYH 错义突变 (R231L)，该突变位于假定的 hMSH6 结合域附近。 R231L 突变蛋白在 A/GO 结合和腺嘌呤糖基化酶活性方面存在严重缺陷。该突变体无法弥补大肠杆菌中的 mutY 缺陷，但不影响与 hMSH6 的结合。这些数据支持 hMYH 通路在癌发生中的作用。 (c) 2006 Elsevier Ireland Ltd. 保留所有权利。
The MutY homolog (MYH) can excise adenines misincorporated opposite to guanines or 7,8-dihydro-8-oxo-guanines (8-oxoG) during DNA replication; thereby preventing G:C to T:A transversions. Germline mutations in the human MYH gene are associated with recessive inheritance of colorectal adenomatous polyposis (MAP). Here, we characterize one newly identified MAP-associated MYH missense mutation (R231L) that lies adjacent to the putative hMSH6 binding domain. The R231L mutant protein has severe defects in A/GO binding and in adenine glycosylase activities. The mutant fails to complement mutY-deficiency in Escherichia coli, but does not affect binding to hMSH6. These data support the role of the hMYH pathway in carcinogenesis. (c) 2006 Elsevier Ireland Ltd. All rights reserved.