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Function of Apollo (SNM1B) at telomere highlighted by a splice variant identified in a patient with Hoyeraal–Hreidarsson syndrome

Abstract : Telomeres, the protein–DNA complexes at the ends of linear chro- mosomes, are protected and regulated by the shelterin molecules, the telomerase complex, and other accessory factors, among which is Apollo, a DNA repair factor of the β-lactamase/β-CASP family. Impaired telomere protection in humans causes dyskeratosis con- genita and Hoyeraal–Hreidarsson (HH) syndrome, characterized by premature aging, bone marrow failure, and immunodeficiency. We identified a unique Apollo splice variant (designated Apollo-Δ) in fibroblasts from a patient with HH syndrome. Apollo- Δ generates a dominant negative form of Apollo lacking the telomeric repeat- binding factor homology (TRFH)-binding motif (TBM) required for interaction with the shelterin TRF2 at telomeres. Apollo-Δ hampers the proper replication of telomeres, leading to major telomeric dys- function and cellular senescence, but maintains its DNA interstrand cross-link repair function in the whole genome. These results iden- tify Apollo as a crucial actor in telomere maintenance in vivo, in- dependent of its function as a general DNA repair factor.
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https://hal.archives-ouvertes.fr/hal-00484901
Contributor : Danielle Thomas <>
Submitted on : Wednesday, May 19, 2010 - 2:34:50 PM
Last modification on : Tuesday, July 28, 2020 - 4:42:02 PM

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  • HAL Id : hal-00484901, version 1

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Fabien Touzot, Isabelle Callebaut, Jean Soulier, Laetitia Gaillard, Chantal Azerrad, et al.. Function of Apollo (SNM1B) at telomere highlighted by a splice variant identified in a patient with Hoyeraal–Hreidarsson syndrome. Proceedings of the National Academy of Sciences of the United States of America , National Academy of Sciences, 2010, 107, pp.10097-102. ⟨hal-00484901⟩

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