HAATI survivors replace canonical telomeres with blocks of generic heterochromatin

Telomeres stabilized without telomerase The ends of eukaryotic chromosomes are composed of repeat sequences known as telomeres. Various proteins bind telomeres to protect them from degradation or inappropriate DNA repair responses, and their length is maintained by a specialized reverse transcriptase, telomerase. Jain et al . show that in the absence of telomerase, telomeres can be maintained by amplifying and recombining heterochromatin sequences there. This process requires histone methylation and two telomere-binding proteins, Pot1 and Ccq1. These findings suggest a mechanism by which cancer cells might escape the requirement for telomerase activation. The ends of eukaryotic chromosomes are composed of repeat sequences known as telomeres. Various proteins bind telomeres to protect them from degradation or inappropriate DNA repair responses, and their length is maintained by a specialized reverse transcriptase, telomerase. These authors show that in the absence of telomerase, telomeres can be maintained by amplifying and recombining heterochromatin sequences there. This process requires histone methylation and two telomere-binding proteins, Pot1 and Ccq1. The notion that telomeres are essential for chromosome linearity stems from the existence of two chief dangers: inappropriate DNA damage response (DDR) reactions that mistake natural chromosome ends for double-strand DNA breaks (DSBs), and the progressive loss of DNA from chromosomal termini due to the end replication problem. Telomeres avert the former peril by binding sequence-specific end-protection factors that control the access of DDR activities 1 , 2 . The latter threat is tackled by recruiting telomerase, a reverse transcriptase that uses an integral RNA subunit to template the addition of telomere repeats to chromosome ends 3 . Here we describe an alternative mode of linear chromosome maintenance in which canonical telomeres are superseded by blocks of heterochromatin. We show that in the absence of telomerase, Schizosaccharomyces pombe cells can survive telomere sequence loss by continually amplifying and rearranging heterochromatic sequences. Because the heterochromatin assembly machinery is required for this survival mode, we have termed it ‘HAATI’ (heterochromatin amplification-mediated and telomerase-independent). HAATI uses the canonical end-protection protein Pot1 (ref. 4 ) and its interacting partner Ccq1 (ref. 5 ) to preserve chromosome linearity. The data suggest a model in which Ccq1