SMARCAD1, a novel human helicase family-defining member associated with genetic instability: Cloning, expression, and mapping to 4q22-q23, a band rich in breakpoints and deletion mutants involved in several human diseases
SMARCAD1, a novel human helicase family-defining member associated with genetic instability: Cloning, expression, and mapping to 4q22-q23, a band rich in breakpoints and deletion mutants involved in several human diseases
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DOI：
10.1006/geno.2000.6281
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发表时间：
2000-10-15
期刊：
影响因子：
4.4
通讯作者：
Drews, R
中科院分区：
文献类型：
--
作者：
Adra, CN;Donato, JL;Drews, R
含DEAD/H盒的解旋酶超家族的成员包括基因组复制、修复和表达所必需的蛋白质。我们在这里报告的克隆和初步鉴定的一个新的人类成员，这个蛋白质家族，指定hHel 1（人类解旋酶1），现在指定SMARCAD 1的雨果。这个含有DEAD/H盒的分子有七个高度保守的序列区域，使我们能够将其置于解旋酶超家族的SNF 2家族中。然而，独特的是，hHel 1含有两个DEAD/H盒基序，这一特性尚未被任何其他SNF 2家族成员所共享。除了这些DEAD/H box/ATP结合基序外，hHel 1还具有推定的核定位信号和可能介导蛋白质-蛋白质相互作用的几个区域。表达分析表明，hHel 1转录是普遍存在的，特别是在内分泌组织中的水平高。我们已经将hHel 1基因定位于人类染色体4 q22-q23;该区域富含与几种人类疾病有关的基因的断点和缺失突变体，特别是软组织平滑肌肉瘤、肝细胞癌和血液恶性肿瘤。我们观察到人类。Hell基因过表达存在于E1 A表达细胞系中，通过基因组重排增加基因再激活事件的能力，表明人Hell可能在遗传不稳定性发展中发挥作用。(C)北京大学出版社.
Members of the DEAD/H box-containing helicase superfamily include proteins essential to genome replication, repair, and expression. We report here the cloning and initial characterization of a novel human member of this protein family, designated hHel1 (human helicase 1), now designated SMARCAD1 by HUGO. This DEAD/H box-containing molecule has seven highly conserved sequence regions that allow us to place it in the SNF2 family of the helicase superfamily, Uniquely, though, hHel1 contains two DEAD/H box motifs, a property not reported to be shared by any other SNF2 family members. This defines a new subfamily consisting of hHel1 and its homologues, In addition to these DEAD/H box/ATP-binding motifs, hHel1 has a putative nuclear localization signal and several regions that may mediate protein-protein interactions. Expression analysis indicates that hHel1 transcripts are ubiquitous, with particularly high levels in endocrine tissue. We have mapped the gene for hHel1 to human chromosome 4q22-q23; this region is rich in breakpoints and deletion mutants of genes involved in several human diseases, notably soft tissue leiomyosarcoma, hepatocellular carcinoma, and hematologic malignancies. Our observation that human. Hell gene overexpression is present in an E1A-expressing cell line with increased capacity for gene reactivation events by genomic rearrangement suggests that human Hell may play a role in genetic instability development. (C) 2000 Academic Press.