The Shelterin TIN2 Subunit Mediates Recruitment of Telomerase to Telomeres

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The shelterin complex protects telomeres from being processed by the DNA damage repair machinery, and also regulates telomerase access and activity at telomeres. The only shelterin subunit known to promote telomerase function is TPP1, which mediates telomerase recruitment to telomeres and stimulates telomerase processivity. Mutations in shelterin components cause Dyskeratosis Congenita (DC) and related disease syndromes due to the inability to maintain telomere homeostasis. In this study, we have identified TIN2-R282H, the most common DC-causing mutation in shelterin subunit TIN2, as a separation-of-function mutant which impairs telomerase recruitment to telomeres, but not chromosome end protection. The telomerase recruitment defect conferred by TIN2-R282H is likely through a mechanism independent of TIN2’s role in anchoring TPP1 at telomeres, since TPP1 localization to telomeres is unaffected by the mutation.

Vyšlo v časopise: The Shelterin TIN2 Subunit Mediates Recruitment of Telomerase to Telomeres. PLoS Genet 11(7): e32767. doi:10.1371/journal.pgen.1005410
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005410

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