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Journal Articles EMBO Journal Year : 2010

SNMIB/Apollo protects leading-strand telomeres against NHEJ-mediated repair

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Abstract

Progressive telomere attrition or deficiency of the protective shelterin complex elicits a DNA damage response as a result of a cell's inability to distinguish dysfunctional telomeric ends from DNA double-strand breaks. SNMIB/Apollo is a shelterin-associated protein and a member of the SMN1/PSO2 nuclease family that localizes to telomeres through its interaction with TRF2. Here, we generated SNMIB/Apollo knockout mouse embryo fibroblasts (MEFs) to probe the function of SNMIB/Apollo at mammalian telomeres. SNMIB/Apollo null MEFs exhibit an increased incidence of G2 chromatid-type fusions involving telomeres created by leading-strand DNA synthesis, reflective of a failure to protect these telomeres after DNA replication. Mutations within SNMIB/Apollo's conserved nuclease domain failed to suppress this phenotype, suggesting that its nuclease activity is required to protect leading-strand telomeres. SNMIB/Apollo−/−ATM−/− MEFs display robust telomere fusions when Trf2 is depleted, indicating that ATM is dispensable for repair of uncapped telomeres in this setting. Our data implicate the 5′-3′ exonuclease function of SNM1B/Apollo in the generation of 3′ single-stranded overhangs at newly replicated leading-strand telomeres to protect them from engaging the non-homologous end-joining pathway.
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Dates and versions

ensl-00817007 , version 1 (23-04-2013)

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  • HAL Id : ensl-00817007 , version 1

Cite

Yung C. Lam, Shamima Akhter, Peili Gu, Jing Ye, Anaïs Poulet, et al.. SNMIB/Apollo protects leading-strand telomeres against NHEJ-mediated repair. EMBO Journal, 2010, 29, pp.2230 - 2241. ⟨ensl-00817007⟩

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