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Fission Yeast Cid12 Has Dual Functions in Chromosome Segregation and Checkpoint Control

机译:裂变酵母Cid12在染色体分离和检查点控制中具有双重功能

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Fission yeast Cid12 is a member of the Cid1 family of specialized poly(A) polymerases. Like cells lacking cid1, cid12Δ mutants were shown to have checkpoint defects when DNA replication was inhibited. Here, we show that Cid12 is also required for faithful chromosome segregation and that mutation of amino acid residues predicted to be essential for poly(A) polymerase activity resulted in loss of Cid12 function in vivo. Cells lacking Cid12 had an increased chromosome segregation failure rate due to precocious loss of sister chromatid cohesion at the centromere but not along the chromosome arms. In keeping with a recently described function for Cid12 in RNA interference (RNAi)-mediated heterochromatin assembly, this was accompanied by an accumulation of polyadenylated transcripts corresponding to naturally silenced repeat elements within heterochromatic domains, with consequent defects in centromeric gene silencing. These cells also suffered increased meiotic defects, and their viability was dependent on the spindle checkpoint protein Bub1. To account for the effects of Cid12 on various aspects of DNA metabolism, including chromosome segregation and the checkpoint control, we suggest that Cid12 has dual functions in RNAi silencing and regulating mRNA stability.
机译:裂变酵母Cid12是专门的poly(A)聚合酶Cid1家族的成员。像缺少 cid1 的细胞一样,当抑制DNA复制时, cid12 Δ突变体也显示出检查点缺陷。在这里,我们表明Cid12也是忠实的染色体分离所必需的,并且预测为poly(A)聚合酶活性必不可少的氨基酸残基突变会导致Cid12体内功能丧失。缺少Cid12的细胞由于在着丝粒处而不是沿着染色体臂的姐妹染色单体内聚力的过早丧失而使染色体分离失败率增加。与最近描述的Cid12在RNA干扰(RNAi)介导的异染色质装配中的功能保持一致,伴随着聚腺苷酸化转录物的积累,对应于异色域中自然沉默的重复元件,从而导致着丝粒基因沉默。这些细胞还遭受了减数分裂缺陷的增加,其生存能力取决于纺锤体检查点蛋白Bub1。为了说明Cid12对DNA代谢各个方面的影响,包括染色体分离和检查点控制,我们建议Cid12在RNAi沉默和调节mRNA稳定性方面具有双重功能。

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