Genome stability in Arabidopsis cells exhibiting alternative lengthening of telomeres

Indefinite proliferation of eukaryotic cells depends on telomerase that counteracts the depletion of DNA from chromosome termini due to the end replication problem. The requirement for telomerase can, under certain conditions, be circumvented by employing homologous recombination-based mechanisms for telomere maintenance. Whereas yeast and mammalian cells lacking telomerase appear to readily adopt alternative telomere lengthening (ALT), in Arabidopsis ALT is inhibited by the Ku heterodimer. Although we failed to establish ALT cell lines from Ku-proficient lines, ALT can be efficiently induced in cells derived from mutants deficient for telomerase reverse transcriptase (TERT) and Ku70. In this study, we describe the growth performance, genome stability and long-term maintenance of telomeric DNA in Arabidopsis ku70 tert ALTcultures. ALT activation increases karyotype stability in the majority of tert ku70 cell lines, which contrasts with ongoing chromosomal rearrangements detected in survival tert cultures that lack any detectable telomeric sequences. Curiously, ku70 tert ALT lines and tert survivor cultures proliferate at a similar rate, although the latter display remarkable chromosomal abnormalities, including giant circular and linear megachromosomes that seem to arise by fusions of multiple chromosomes. This observation underlies the extraordinary tolerance of plant cells to telomere dysfunction.