YNK1, the yeast homolog of human metastasis suppressor NM23, is required for repair of UV radiation- and etoposide-induced DNA damage
YNK1, the yeast homolog of human metastasis suppressor NM23, is required for repair of UV radiation- and etoposide-induced DNA damage
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DOI：
10.1016/j.mrfmmm.2008.09.015
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发表时间：
2009-01-15
影响因子：
2.3
通讯作者：
Kaetzel, David M.
中科院分区：
文献类型：
--
作者：
Yang, Mengmeng;Jarrett, Stuart G.;Kaetzel, David M.
在人类中，NM23-H1是一种转移抑制因子，它在转移性黑色素瘤和乳腺癌细胞中的表达降低，并且具有抑制转移生长的能力，而不会对转化的表型产生显著影响。NM23-H1在体外表现出三种酶活性，每种酶都具有维持基因组稳定性的潜力，分别是一个3‘-5’外切酶和两个激酶，即核苷二磷酸激酶(NDPK)和蛋白组氨酸激酶。在此，我们研究了NM23蛋白对酿酒酵母DNA修复的潜在贡献。该基因含有单一的NM23同源基因YNK1。消融YNK1可使紫外线和依托泊苷诱导的DNA损伤修复延迟3~6h，但YNK1对MMS诱导的DNA修复动力学有110个影响。此外，线粒体DNA损伤的修复不需要YNK1。为了确定核DNA修复缺陷是否表现为突变频率的增加，采用了CAN1正向试验。YNK1缺失与紫外线(2.6倍)或MMS(1.6倍)处理后的突变率增加有关。突变光谱分析进一步显示，紫外线处理后，ynk1 Delta菌株的碱基替换率和移码突变率显著增加。本研究表明了YNK1在酵母DNA修复中的一个新的作用，并提示了一个抗突变功能，可能与NM23-H1在人类中的转移抑制功能有关。(C)2008爱思唯尔B.V.保留所有权利。
In humans, NM23-H1 is a metastasis Suppressor whose expression is reduced in metastatic melanoma and breast carcinoma cells, and which possesses the ability to inhibit metastatic growth Without Significant impact on the transformed phenotype. NM23-H1 exhibits three enzymatic activities in vitro, each with potential to maintain genomic stability, a 3'-5' exonuclease and two kinases, nucleoside diphosphate kinase (NDPK), and protein histidine kinase. Herein we have investigated the potential contributions of NM23 proteins to DNA repair in the yeast, Saccharomyces cerevisiae. which contains a single NM23 homolog, YNK1. Ablation of YNK1 delayed repair of UV- and etoposide-induced nuclear DNA damage by 3-6 h. However, YNK1 had 110 impact upon the kinetics of MMS-induced DNA repair. Furthermore, YNK1 Was not required for repair of mitochondrial DNA damage. To determine whether the nuclear DNA repair deficit manifested as an increase in mutation frequency, the CAN1 forward assay was employed. An YNK1 deletion was associated with increased mutation rates following treatment with either UV (2.6x) or MMS (1.6x). Mutation spectral analysis further revealed significantly increased rates of base substitution and frameshift mutations following UV treatment in the ynk1 Delta strain. This Study indicates a novel role for YNK1 in DNA repair in yeast, and suggests an anti-mutator function that may contribute to the metastasis suppressor function of NM23-H1 in humans. (c) 2008 Elsevier B.V. All rights reserved.