EXOG, a novel paralog of Endonuclease G in higher eukaryotes.

EXOG, a novel paralog of Endonuclease G in higher eukaryotes.
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DOI:
10.1093/nar/gkm1169
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发表时间:
2008-03
影响因子:
14.9
通讯作者:
Meiss G
Meiss G
中科院分区:
生物学2区
文献类型:
--
作者:
Cymerman IA;Chung I;Beckmann BM;Bujnicki JM;Meiss G

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进化保守的线粒体核酸酶参与低等和高等真核生物的程序性细胞死亡和正常细胞增殖。内切/外切核酸酶Nuc 1 p,也称为“酵母内切核酸酶G(EndoG β)”,是这类酶的成员,其不同于哺乳动物同源物,除了其广谱内切核酸酶活性之外,还存在5′-3′外切核酸酶活性。然而,这种外切核酸酶活性被认为是酵母酶在DNA重组和修复中的功能所必需的。在这里,我们表明,高等真核生物除了EndoG含有它的partial 'EXOG',一种新的EndoG样线粒体内切/外切核酸酶。我们发现,在后生动物的进化过程中,复制的祖先核酸酶基因显然产生了旁系同源的EndoG-和EXOG-蛋白质亚科在高等真核生物,从而保持完整的内切/外切核酸酶活性发现在线粒体的较低的真核生物。我们证明,人EXOG是一种二聚体线粒体酶,显示5′-3′核酸外切酶活性,并进一步不同于EndoG的底物特异性。我们推测,在高等真核生物中,EndoG和EXOG的互补酶活性可能共同解释了保守的线粒体内切/外切核酸酶的致死和重要功能。
Evolutionary conserved mitochondrial nucleases are involved in programmed cell death and normal cell proliferation in lower and higher eukaryotes. The endo/exonuclease Nuc1p, also termed ‘yeast Endonuclease G (EndoG)’, is a member of this class of enzymes that differs from mammalian homologs by the presence of a 5′–3′ exonuclease activity in addition to its broad spectrum endonuclease activity. However, this exonuclease activity is thought to be essential for a function of the yeast enzyme in DNA recombination and repair. Here we show that higher eukaryotes in addition to EndoG contain its paralog ‘EXOG’, a novel EndoG-like mitochondrial endo/exonuclease. We find that during metazoan evolution duplication of an ancestral nuclease gene obviously generated the paralogous EndoG- and EXOG-protein subfamilies in higher eukaryotes, thereby maintaining the full endo/exonuclease activity found in mitochondria of lower eukaryotes. We demonstrate that human EXOG is a dimeric mitochondrial enzyme that displays 5′–3′ exonuclease activity and further differs from EndoG in substrate specificity. We hypothesize that in higher eukaryotes the complementary enzymatic activities of EndoG and EXOG probably together account for both, the lethal and vital functions of conserved mitochondrial endo/exonucleases.
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