Telomere exchange and asymmetric segregation of chromosomes can account for the unlimited proliferative potential of ALT cell populations.
Telomerase-negative cancer cells show increased telomere sister chromatid exchange (T-SCE) rates, a phenomenon that has been associated with an alternative lengthening of telomeres (ALT) mechanism for maintaining telomeres in this subset of cancers. Here we examine whether or not T-SCE can maintain telomeres in human cells using a combinatorial model capable of describing how telomere lengths evolve over time. Our results show that random T-SCE is unlikely to be the mechanism of telomere maintenance of ALT human cells, but that increased T-SCE rates combined with a recently proposed novel mechanism of non-random segregation of chromosomes with long telomeres preferentially into the same daughter cell during cell division can stabilize chromosome ends in ALT cancers. At the end we discuss a possible experiment that can validate the findings of this study.
Blagoev
Krastan B
KB
Los Alamos National Laboratory, Los Alamos, NM 87544, USA. kblagoev@nsf.gov
Goodwin
Edwin H
EH
D049109:Cell Proliferation; D020090:Chromosome Segregation / Q000235:genetics / Q000502:physiology*; D003198:Computer Simulation; D006801:Humans; D008957:Models, Genetic; D012854:Sister Chromatid Exchange / Q000235:genetics / Q000502:physiology*; D016615:Telomere / Q000235:genetics / Q000502:physiology*