The Impact of XRCC5 and LINE-1 Retrotransposons on Telomere Maintenance

摘要

Telomere maintenance is required for long-term growth of tumor cells. In most tumors, telomeres are maintained by the enzyme telomerase; however, about 10% of cancers are able to maintain telomeres without telomerase using recombination-based mechanisms. Our lab focuses on understanding whether this mechanism of telomere recombination in mammalian cells involves retrotransposons. To determine if retrotransposons contribute to telomere maintenance we are using cells deleted for XRCC5, which encodes for the DNA repair protein Ku80. Ku80 is required for non-homologous end-joining, and during B- and T- cell development, due to its role in V(D) J recombination. Using an assay for LINE-1 retrotransposition that can detect insertions adjacent to telomere and subtelomere sequences, we find that LINE-1 elements with both an intact and mutant endonuclease domain, can insert into telomere repeats in cells lacking Ku80.