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Fission Yeast Pot1 and RecQ Helicase Are Required for Efficient Chromosome Segregation

机译:裂变酵母Pot1和RecQ解旋酶是有效的染色体分离所必需的

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Pot1 is a single-stranded telomere-binding protein that is conserved from fission yeast to mammals. Deletion of Schizosaccharomyces pombe pot1+ causes immediate telomere loss. S. pombe Rqh1 is a homolog of the human RecQ helicase WRN, which plays essential roles in the maintenance of genomic stability. Here, we demonstrate that a pot1Δ rqh1-hd (helicase-dead) double mutant maintains telomeres that are dependent on Rad51-mediated homologous recombination. Interestingly, the pot1Δ rqh1-hd double mutant displays a “cut” (cell untimely torn) phenotype and is sensitive to the antimicrotubule drug thiabendazole (TBZ). Moreover, the chromosome ends of the double mutant do not enter the pulsed-field electrophoresis gel. These results suggest that the entangled chromosome ends in the pot1Δ rqh1-hd double mutant inhibit chromosome segregation, signifying that Pot1 and Rqh1 are required for efficient chromosome segregation. We also found that POT1 knockdown, WRN-deficient human cells are sensitive to the antimicrotubule drug vinblastine, implying that some of the functions of S. pombe Pot1 and Rqh1 may be conserved in their respective human counterparts POT1 and WRN.
机译:Pot1是一种单链端粒结合蛋白,从裂变酵母到哺乳动物都是保守的。删除粟酒裂殖酵母pot1 + 会立即导致端粒丢失。 S。 pombe Rqh1是人类RecQ解旋酶WRN的同源物,在维持基因组稳定性方面起着至关重要的作用。在这里,我们证明了pot1Δrqh1-hd (解旋酶死亡)双重突变体维持依赖于Rad51介导的同源重组的端粒。有趣的是,pot1Δrqh1-hd 双重突变体表现出“切割”(细胞不合时宜地撕裂)表型,并且对抗微管药物噻苯达唑(TBZ)敏感。而且,双突变体的染色体末端不进入脉冲场电泳凝胶。这些结果表明,在pot1Δrqh1-hd 双突变体中纠缠的染色体末端抑制了染色体的分离,这表明Pot1和Rqh1是有效的染色体分离所必需的。我们还发现,敲低WRN的人细胞POT1对抗微管药物长春碱敏感,这暗示了 S的某些功能。 pombe Pot1和Rqh1可以在相应的人类对应物POT1和WRN中保存。

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