Habib Ahmed G K, Sugiura Kanako, Ueno Masaru
Department of Molecular Biotechnology, Graduate School of Advanced Sciences of Matter, Hiroshima University, Kagamiyama, Higashi-Hiroshima, Japan.
Department of Biotechnology and Life Sciences, Faculty of Postgraduate Studies for Advanced Sciences (PSAS), Beni-Suef University, Beni-Suef, Egypt.
PLoS One. 2018 Jan 3;13(1):e0190523. doi: 10.1371/journal.pone.0190523. eCollection 2018.
Ring chromosomes are circular chromosomal abnormalities that have been reported in association with some genetic disorders and cancers. In Schizosaccharomyces pombe, lack of function of protection of telomere 1 (Pot1) or telomerase catalytic subunit (Trt1) results in survivors with circular chromosomes. Hitherto, it is poorly understood how cells with circular chromosomes survive and how circular chromosomes are maintained. Fission yeast Cut17/Bir1, Ark1, Pic1, and Nbl1 is a conserved chromosome passenger complex (CPC) functioning mainly throughout mitosis. Here, using a temperature-sensitive mutant of CPC subunits, we determined that CPC is synthetically lethal in combination with either Pot1 or Trt1. The pot1Δ pic1-T269 double mutant, which has circular chromosomes, showed a high percentage of chromosome mis-segregation and DNA damage foci at 33°C. We furthermore found that neither Shugoshin Sgo2 nor heterochromatin protein Swi6, which contribute to the centromeric localization of CPC, were required for the survival in the absence of Pot1. Both the pot1Δ sgo2Δ and pot1Δ swi6Δ double mutants displayed a high percentage of DNA damage foci, but a low percentage of chromosome mis-segregation, suggesting the link between the high percentage of chromosome mis-segregation and the lethality of the CPC pot1Δ double mutant. Our results suggest that CPC is required for the survival of cells with circular chromosomes and sheds light on the possible roles of CPC in the maintenance of circular chromosomes.
环状染色体是一种环状染色体异常,已被报道与一些遗传疾病和癌症有关。在粟酒裂殖酵母中,端粒保护蛋白1(Pot1)或端粒酶催化亚基(Trt1)功能缺失会导致产生带有环状染色体的存活细胞。迄今为止,人们对带有环状染色体的细胞如何存活以及环状染色体如何维持了解甚少。裂殖酵母Cut17/Bir1、Ark1、Pic1和Nbl1是一种保守的染色体乘客复合体(CPC),主要在整个有丝分裂过程中发挥作用。在这里,我们使用CPC亚基的温度敏感突变体,确定CPC与Pot1或Trt1联合存在时具有合成致死性。具有环状染色体的pot1Δ pic1-T269双突变体在33°C时显示出高比例的染色体错分离和DNA损伤灶。我们还发现,在没有Pot1的情况下,对CPC着丝粒定位有贡献的守护蛋白Sgo2和异染色质蛋白Swi6都不是细胞存活所必需的。pot1Δ sgo2Δ和pot1Δ swi6Δ双突变体都显示出高比例的DNA损伤灶,但染色体错分离比例较低,这表明高比例的染色体错分离与CPC pot1Δ双突变体的致死性之间存在联系。我们的结果表明,CPC是带有环状染色体的细胞存活所必需的,并揭示了CPC在维持环状染色体中的可能作用。