The N-terminal region of the Schizosaccharomyces pombe RecQ helicase, Rqh1p, physically interacts with Topoisomerase III and is required for Rqh1p function
The N-terminal region of the Schizosaccharomyces pombe RecQ helicase, Rqh1p, physically interacts with Topoisomerase III and is required for Rqh1p function
复制标题
DOI：
10.1007/s00438-005-1111-3
复制
发表时间：
2005-03-01
影响因子：
3.1
通讯作者：
Stewart, E
中科院分区：
文献类型：
--
作者：
Ahmad, F;Stewart, E
粟酒裂殖酵母rqh 1（+）基因编码RecQ DNA解旋酶家族的成员。该蛋白质家族的成员对于维持遗传完整性至关重要。因此，编码人RecQ同源物Blm、Recn和RecQ 4的基因突变分别引起Bloom综合征、Werner综合征和Rothmund-Thomson综合征--由基因组不稳定性引起的疾病. S.缺乏功能性rqh 1+基因的粟酒裂殖酵母细胞表现出降低的生存力，并表现出有缺陷的染色体分离，特别是在UV照射或S期停滞后。在这项研究中，我们使用了一个rqh 1+删除系列，以表明，N-末端部分的Rqh 1是必不可少的Rqh 1功能。此外，Rqh 1的保守解旋酶和RNaseD C-末端（HRDC）结构域也在允许细胞耐受暴露于DNA损伤剂和S-期抑制剂羟基脲（HU）中起作用。我们还证明，拓扑异构酶III（Top3）结合到Rqh 1的前322个N-末端氨基酸内的一个位点，这种结合与Rqh 1功能相关。对rqh 1（-）top3 Delta突变体的遗传分析表明，在功能性或部分功能性Rqh 1蛋白存在下，Top3是维持基因组完整性和细胞活力所必需的。
The Schizosaccharomyces pombe rqh1(+) gene encodes a member of the RecQ DNA helicase family. Members of this protein family are essential for the maintenance of genetic integrity. Thus, mutations in the genes encoding the human RecQ homologues Blm, Wrn and RecQ4 cause Bloom syndrome, Werner syndrome and Rothmund - Thomson syndrome, respectively - diseases which result from genome instability. S. pombe cells that lack a functional rqh1+ gene show reduced viability and display defective chromosome segregation, particularly after UV irradiation or S- phase arrest. In this study we used an rqh1+ deletion series to show that the N- terminal portion of Rqh1 is essential for Rqh1 function. Moreover, the conserved Helicase and RNaseD C-terminal (HRDC) domain of Rqh1 also plays a role in allowing cells to tolerate exposure to DNA damaging agents and the S- phase inhibitor hydroxyurea (HU). We also demonstrate that Topoisomerase III (Top3) binds to a site within the first 322 N- terminal amino acids of Rqh1 and that this binding correlates with Rqh1 function. Genetic analysis of rqh1(-) top3 Delta mutants reveals that, in the presence of functional or partially functional Rqh1 protein, Top3 is required to maintain genome integrity and cell viability.