Telomere maintenance by recombination in human cells

Abstract

Telomeres of eukaryotic chromosomes contain many tandem repeats of a G-rich sequence (for example, TTAGGG in vertebrates¹). In most normal human cells, telomeres shorten with each cell division, and it is proposed that this limits the number of times these cells can replicate². Telomeres may be maintained in germline cells, and in many immortalized cells and cancers, by the telomerase holoenzyme³ (first discovered in the ciliate Tetrahymena⁴), which uses an RNA subunit as template for synthesis of telomeric DNA by the reverse transcriptase catalytic subunit⁵. Some immortalized human cell lines and some tumours maintain their telomeres in the absence of any detectable telomerase activity by a mechanism referred to as alternative lengthening of telomeres^6,7 (ALT). Here we show that DNA sequences are copied from telomere to telomere in an immortalized human ALT cell line, indicating that ALT occurs by means of homologous recombination and copy switching.