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Circular chromosome formation in a fission yeast mutant defective in two ATM homologues

Abstract

Telomeres, found at chromosomal ends, are essential for stable maintenance of linear chromosomes in eukaryotes. The ATM family of genes, including budding yeast TEL1 (Refs 1, 2 ), fission yeast rad3+ ( ref. 3 ) and human ATM (ref. 4 ), have been reported to be involved in telomere length regulation5,6,7 although the significance of the telomere phenotypes observed with the mutated genes remains elusive. We have cloned tel1+, another fission yeast ATM homologue, and found that a tel1rad3 double mutant lost all telomeric DNA sequences. Thus, the ATM homologues are essential in telomere maintenance. The mutant grew poorly and formed irregular-shaped colonies, probably due to chromosome instability, however, during prolonged culture of the double mutant, cells forming normal round-shaped colonies arose at a relatively high frequency. All three chromosomes in these derivative cells were circular and lacked telomeric sequences. To our knowledge, this is the first report of eukaryotic cells whose chromosomes are all circular. Upon meiosis, these derivative cells produced few viable spores. Therefore, the exclusively circular genome lacking telomeric sequences is proficient for mitotic growth, but does not permit meiosis.

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Figure 1: Telomere length of ATM-homologue mutants.
Figure 2: Phenotypic alteration in ATM-deficient strains.
Figure 3: PFGE separation of the chromosomes of ATM-homologue disruptants.
Figure 4: Identification of the PCR products containing the head-to-head fusion of the two subtelomeric rDNA repeats of chromosome III.
Figure 5: Circular chromosomes visualized in M-phase arrested cells.

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Acknowledgements

We thank E.A. Kamei, T. Shibata and L. Guarente for critical reading of and comments on the manuscript, N. Munakata for γ-ray irradiation experiments and O. Niwa for providing the nda3-KM311 mutant and for helpful discussion. The excellent secretarial work of M. Fukuda is acknowledged. This work was supported by a Grant-in-Aid for Cancer Research and a Grant-in-Aid for Scientific Research on Priority Areas from the Ministry of Education, Science, Sports and Culture of Japan, a Grant-in-Aid of Special Coordination Funds for Promoting Science and Technology from the Science and Technology Agency of Japan and a Grant-in-Aid from the Mitsubishi Foundation. T.N. was supported by a JSPS Research Fellowship for Young Scientists.

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Correspondence to Fuyuki Ishikawa.

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Naito, T., Matsuura, A. & Ishikawa, F. Circular chromosome formation in a fission yeast mutant defective in two ATM homologues. Nat Genet 20, 203–206 (1998). https://doi.org/10.1038/2517

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