Mre11 and Blm-Dependent Formation of ALT-Like Telomeres in Ku-Deficient

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The majority of cancer cells use a special enzyme called telomerase to maintain telomeres. However, some cancer cells do not possess telomerase and use instead the so-called ALT mechanism to maintain telomeres. ALT is a complex pathway that entails the action of many factors, and the telomere DNAs of ALT cancer cells are extremely abnormal (e.g., they are often detached from the rest of the chromosomes and often exist in single-stranded forms). Currently, there are few manipulations that one can use to induce normal cells to engage in the ALT mechanism. The lack of a good “model” system poses a major obstacle to the understanding of this pathway and the development of effective counter-measures against ALT cancer cells. By removing Ku and a checkpoint factor from U. maydis (a yeast-like fungus), we generated clones that exhibit many of the characteristic abnormalities of ALT cancer cells. Moreover, we identified two factors (i.e., Mre11 and Blm) that when deleted, abolished the ALT phenotypes. Further analysis of this model may lead to the development of new strategies for shrinking the telomeres of cancer cells, thereby arresting their proliferation.

Vyšlo v časopise: Mre11 and Blm-Dependent Formation of ALT-Like Telomeres in Ku-Deficient. PLoS Genet 11(10): e32767. doi:10.1371/journal.pgen.1005570
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005570

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