Frequent recombination in telomeric DNA may extend the proliferative life of telomerase-negative cells.
For cells on the path to carcinogenesis, the key to unlimited growth potential lies in overcoming the steady loss of telomeric sequence commonly referred to as the 'end-replication problem' that occurs with each cell division. Most human tumors have reactivated telomerase, a specialized reverse transcriptase that directs RNA-templated addition of telomeric repeats on to chromosomal termini. However, approximately 10% of tumors maintain their telomeres through a recombination-based mechanism, termed alternative lengthening of telomeres or ALT. Here we demonstrate that telomeric DNA undergoes a high rate of a particular type of recombination visualized cytogenetically as sister chromatid exchange (SCE), and that this rate is dependent on genotype. A novel model of ALT is presented in which it is argued that telomeric exchanges, if they are unequal and occur at a sufficiently high frequency, will allow cells to proliferate indefinitely without polymerase-mediated extension of telomeric sequence.
Bailey
Susan M
SM
Department of Environmental and Radiological Health Sciences, Colorado State University, Fort Collins, CO 80523, USA.
Brenneman
Mark A
MA
Goodwin
Edwin H
EH
D000818:Animals; D002455:Cell Division; D002478:Cells, Cultured; D016922:Cellular Senescence; D004247:DNA / Q000235:genetics; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011995:Recombination, Genetic; D012854:Sister Chromatid Exchange; D019098:Telomerase / Q000032:analysis; D016615:Telomere / Q000235:genetics*
D004247:DNA; D019098:Telomerase