Suppressors of Bir1p (Survivin) identify roles for the chromosomal passenger protein Pic1p (INCENP) and the replication initiation factor Psf2p in chromosome segregation
Suppressors of Bir1p (Survivin) identify roles for the chromosomal passenger protein Pic1p (INCENP) and the replication initiation factor Psf2p in chromosome segregation
复制标题
DOI：
10.1128/mcb.25.20.9000-9015.2005
复制
发表时间：
2005-10-01
影响因子：
5.3
通讯作者：
Hunter, T
中科院分区：
文献类型：
--
作者：
Huang, HK;Bailis, JM;Hunter, T
裂殖酵母 Bir1p/Cut17p/Pbh1p 是人生存素的同源物，是细胞分裂和胞质分裂所需的保守染色体过客蛋白。为了研究 Bir1p 如何促进染色体的精确分离，我们生成并分析了温度敏感等位基因 bir1-46，并进行遗传筛选以寻找与 bir1(+) 相互作用的基因。我们鉴定出 Psf2p（DNA 复制启动所需的 GINS 复合物的一个组成部分）是 bir1-46 生长缺陷的高拷贝数抑制因子。通过耗尽或删除或使用温度敏感等位基因 psf2-209 导致 Psf2p 功能丧失，导致染色体错误分离，这与 Bir1p 的错误定位相关。我们还发现 Psf2p 的人类同源物 PSF2 是正确染色体分离所必需的。此外，我们观察到 Pic1p（INCENP（内着丝粒蛋白）的裂殖酵母同源物）的高拷贝数表达抑制了 bir1-46。 Pic1p 表现出染色体过客蛋白的典型定位模式。 pic1(+) 的缺失导致与 bir1-46 类似的染色体错误分离表型。我们的数据表明，Bir1p 和 Pic1p 作为保守染色体乘客复合体的一部分，并且 Psf2p/GINS 可能通过着丝粒复制中的 S 期作用间接影响该复合体在染色体分离中的定位和功能。
Fission yeast Bir1p/Cut17p/Pbh1p, the homolog of human Survivin, is a conserved chromosomal passenger protein that is required for cell division and cytokinesis. To study how Bir1p promotes accurate segregation of chromosomes, we generated and analyzed a temperature-sensitive allele, bir1-46, and carried out genetic screens to find genes that interact with bir1(+). We identified Psf2p, a component of the GINS complex required for DNA replication initiation, as a high-copy-number suppressor of the bir1-46 growth defect. Loss of Psf2p function by depletion or deletion or by use of a temperature-sensitive allele, psf2-209, resulted in chromosome missegregation that was associated with mislocalization of Bir1p. We also found that the human homolog of Psf2p, PSF2, was required for proper chromosome segregation. In addition, we observed that high-copy-number expression of Pic1p, the fission yeast homolog of INCENP (inner centromere protein), suppressed bir1-46. Pic1p exhibited a localization pattern typical of chromosomal passenger proteins. Deletion of pic1(+) caused chromosome missegregation phenotypes similar to those of bir1-46. Our data suggest that Bir1p and Pic1p act as part of a conserved chromosomal passenger complex and that Psf2p/GINS indirectly affects the localization and function of this complex in chromosome segregation, perhaps through an S-phase role in centromere replication.