Chromosome passenger complex is required for the survival of cells with ring chromosomes in fission yeast

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.

Ring chromosome 15 – cytogenetics and mapping arrays: a case report and review of the literature

“…They have been identified for all human chromosomes [ 2 ]. Ring formation often results from terminal breaks in both chromosome arms, followed by a fusion event of the broken ends [ 1 , 3 ]. As a result, genetic material may or may not be lost, leading to different types of rings [ 2 ].…”

“…Sister chromatid exchanges due to cell mistakes during mitosis can result in chromosomal abnormalities that produce dicentric rings, interlocked rings, or ring loss leading to monosomy or mosaicism [ 4 , 5 ]. Furthermore, transmission of unstable rings can lead to de novo ring formations in the next generation [ 2 , 3 , 6 ].…”

Shugoshin Regulates Cohesin, Kinetochore-Microtubule Attachments, and Chromosomal Instability

“…Mammalian shugoshin is associated with PP2A and chromosomal passenger complex (CPC) at centromeres [Suzuki et al, 2006;Asai et al, 2019]. CPC is a critical participant that guarantees the appropriate chromosome separation to avoid chromosomal instability (CIN) and aneuploidy [Habib et al, 2018]. Shugoshin promotes CPC recruitment to centromeres by binding to borealin (Fig.…”

“…2) [Wang et al, 2021], which ensures kinetochore attachment to microtubules emanating from bipolar spindles, thereby facilitating the correction of improper attachment on the mitotic spindle (Table 2) [Kobayashi and Kawashima, 2019;Sane et al, 2021]. The CPC can dissolve kineto-chore-microtubule mis-attachment through phosphorylating several substrates and is one of the highly conserved complexes that sense the lack of kinetochore-microtubule tension (Table 2) [Habib et al, 2018;Cairo and Lacefield, 2020;Wang et al, 2021]. The resulting unconnected kinetochore activates the SAC, stabilizes securin and inhibits separase, thereby delaying entry into anaphase II to ensure proper kinetochore-microtubule attachments (Fig.…”

Complex karyotype in myelodysplastic syndromes: Diagnostic procedure and prognostic susceptibility

“…Ring chromosome (RC) is a circular DNA molecule 36 formed by merging of two broken ends of a chromosome, a broken end with the end of telomeres of a chromosome, or the two ends of telomeres of a chromosome. 37 RC is a rare disorder; However, in 75% of AML patients and 97% of MDS patients holder RC mutation, the CK [such as der (9p), der (12) dic (12 ;?19), +15, - 18] have been observed.…”