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Retinoblastoma Protein Enhances the Fidelity of Chromosome Segregation Mediated by hsHec1p

机译:视网膜母细胞瘤蛋白增强hsHec1p介导的染色体分离保真度

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Retinoblastoma protein (Rb) plays important roles in cell cycle progression and cellular differentiation. It may also participate in M phase events, although heretofore only circumstantial evidence has suggested such involvement. Here we show that Rb interacts, through an IxCxE motif and specifically during G2/M phase, with hsHec1p, a protein essential for proper chromosome segregation. The interaction between Rb and hsHec1p was reconstituted in a yeast strain in which human hsHEC1 rescues the null mutation of scHEC1. Expression of Rb reduced chromosome segregation errors fivefold in yeast cells sustained by a temperature-sensitive (ts) hshec1-113 allele and enhanced the ability of wild-type hsHec1p to suppress lethality caused by a ts smc1mutation. The interaction between Hec1p and Smc1p was important for the specific DNA-binding activity of Smc1p. Expression of Rb restored part of the inactivated function of hshec1-113p and thereby increased the DNA-binding activity of Smc1p. Rb thus increased the fidelity of chromosome segregation mediated by hsHec1p in a heterologous yeast system.
机译:视网膜母细胞瘤蛋白(Rb)在细胞周期进程和细胞分化中起重要作用。它可能也参与了M期事件,尽管迄今为止只有间接证据表明参与了该阶段。在这里,我们显示Rb通过IxCxE基序,特别是在G 2 / M阶段,与hsHec1p相互作用,hsHec1p是正确染色体分离所必需的蛋白质。在人hs HEC1 拯救了sc HEC1 的无效突变的酵母菌株中,Rb与hsHec1p之间的相互作用得以重建。 Rb的表达将温度敏感的(ts)hs hec1-113 等位基因维持的酵母细胞中的染色体分离错误降低了五倍,并增强了野生型hsHec1p抑制ts smc1 突变。 Hec1p和Smc1p之间的相互作用对于Smc1p的特定DNA结合活性很重要。 Rb的表达恢复了hshec1-113p失活功能的一部分,从而增加了Smc1p的DNA结合活性。因此,Rb增加了由hsHec1p介导的异源酵母系统中染色体分离的保真度。

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