AKTIP/Ft1, a New Shelterin-Interacting Factor Required for Telomere Maintenance

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Chromosome ends are capped by specialized structures called telomeres, which protect chromosomes from deterioration, incomplete replication and end-to-end fusion. Defects in telomere structure and/or function may have a strong impact on human health, leading to premature aging and a variety of diseases including cancer. One of the most important tasks to understand and possibly prevent the consequences of telomere dysfunction is the identification and characterization of telomere-associated proteins. Here we show for the first time that human telomeric proteins can be identified on the basis of their homology with those that protect the telomeres of the fruit fly Drosophila melanogaster. Although flies and humans elongate their telomeres through different mechanisms, our studies suggested that a subset of Drosophila telomere-associated proteins have conserved human counterparts. Based on this hypothesis we identified and characterized a novel human telomeric protein called AKTIP. We show that AKTIP binds the components of the shelterin multiprotein complex, which caps and protects the human telomeres. AKTIP-depleted chromosomes exhibit an accumulation of DNA repair factors at their ends (telomere dysfunction foci), which are diagnostic of telomere damage. Loss of AKTIP results in a general impairment of DNA synthesis and in defective telomere replication. Collectively, our results indicate that AKTIP cooperates with the shelterin component TRF1 to ensure proper telomere replication.

Vyšlo v časopise: AKTIP/Ft1, a New Shelterin-Interacting Factor Required for Telomere Maintenance. PLoS Genet 11(6): e32767. doi:10.1371/journal.pgen.1005167
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005167

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