Abstract
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.
Highlights
Ring chromosomes are circular DNA molecules that can be formed either by DNA-double strand breaks at both arms of a chromosome, which generates sticky ends ready for fusion [1,2,3], or by telomere dysfunction as a result of telomere uncapping [4,5,6]
We find that the lack of function of chromosome passenger complex (CPC) was lethal to fission yeast pot1Δ and trt1Δ cells with circular chromosomes
We found that all double mutants retaining the protection of telomere 1 (Pot1) plasmid could grow
Summary
Ring chromosomes are circular DNA molecules that can be formed either by DNA-double strand breaks at both arms of a chromosome, which generates sticky ends ready for fusion [1,2,3], or by telomere dysfunction as a result of telomere uncapping [4,5,6]. Ring chromosomes are rare in general, they affect the cells in which they are present. Ring chromosomes are associated with various clinical phenotypes such as craniofacial dysmorphisms, intellectual disability, growth retardation, and epileptic seizures [7, 8]. CPC is required for ring chromosome maintenance analysis, decision to publish, or preparation of the manuscript
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