Disruption of the Rev3l-encoded catalytic subunit of polymerase ζ in mice results in early embryonic lethality
Disruption of the Rev3l-encoded catalytic subunit of polymerase ζ in mice results in early embryonic lethality
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DOI：
10.1016/s0960-9822(00)00726-0
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发表时间：
2000-10-05
期刊：
影响因子：
9.2
通讯作者：
Rajewsky, K
中科院分区：
文献类型：
--
作者：
Esposito, G;Godin, I;Rajewsky, K
聚合酶 zeta>(*) over bar * (Pol zeta) 是一种容易出错的 DNA 聚合酶 [1]，在酵母中参与跨损伤合成 (TLS)，并负责大多数紫外线 (UV) 辐射诱导和自发突变 [2-4]。 Pol zeta 由三个亚基组成：REV1，一种脱氧胞苷基转移酶 [5]； REV7，功能不清楚[6]； REV3 是催化亚基，单独使用 REV3 就足以进行 TLS，但与 REV1 和 REV7 结合可增强其活性 [5,7]。使用经紫外线辐射处理的人类细胞进行的实验还表明，哺乳动物 Pl 5 参与 TLS [7]，Pol zeta [4,7,8] 的特殊诱变活性表明其可能在免疫球蛋白 tig) 基因的体细胞超突变中发挥作用 [9]。在这里，我们报告说，与酵母中REV3基因对生命不是必需的[4]不同，小鼠同源物(Rev31)的破坏导致早期胚胎致死，在Rev31(-/-)胚胎中，卵黄囊中无法识别出除红细胞以外的造血细胞，Rev31(-/-)造血前体细胞无法在体外扩增，并且不能衍生出造血细胞。 Rev31(-/-)胚胎不能获得成纤维细胞，也不能获得Rev31(-/-)胚胎干(ES)细胞。这是第一个证据表明 TLS 中涉及的酶对于哺乳动物的发育至关重要。 (C) 2000 Elsevier Science Ltd. 保留所有权利。
Polymerase zeta>(*) over bar * (Pol zeta) is an error-prone DNA polymerase [1], which in yeast is involved in trans-lesion synthesis (TLS) and is responsible for most of the ultraviolet (UV) radiation-induced and spontaneous mutagenesis [2-4]. Pol zeta consists of three subunits: REV1, a deoxycytidyl-transferase [5]; REV7, of unclear function [6]; and REV3, the catalytic subunit, REV3 alone is sufficient to carry out TLS, but association with REV1 and REV7 enhances its activity [5,7]. Experiments using human cells treated with UV radiation indicate also that mammalian Pl 5 is involved in TLS [7], The peculiar mutagenic activity of Pol zeta [4,7,8] suggests a possible role in somatic hypermutation of immunoglobulin tig) genes [9]. Here, we report that, unlike in yeast where the REV3 gene is not essential for life [4], disruption of the mouse homologue (Rev31) resulted in early embryonic lethality, In Rev31(-/-) embryos, no haematopoietic cells other than erythrocytes could be identified in the yolk sac, Rev31(-/-) haematopoietic precursors were unable to expand in vitro and no haematopoietic cells could be derived from the intraembryonic haematogenic compartment (splanchnopleura), Fibroblasts could not be derived from the Rev31(-/-) embryos, and Rev31(-/-) embryonic stem (ES) cells could not be obtained. This is the first evidence that an enzyme involved in TLS is critical for mammalian development. (C) 2000 Elsevier Science Ltd. All rights reserved.