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Medientyp:
E-Artikel
Titel:
Function of Apollo (SNM1B) at telomere highlighted by a splice variant identified in a patient with Hoyeraal–Hreidarsson syndrome
Beteiligte:
Touzot, Fabien;
Callebaut, Isabelle;
Soulier, Jean;
Gaillard, Laetitia;
Azerrad, Chantal;
Durandy, Anne;
Fischer, Alain;
de Villartay, Jean-Pierre;
Revy, Patrick
Erschienen:
Proceedings of the National Academy of Sciences, 2010
Erschienen in:
Proceedings of the National Academy of Sciences, 107 (2010) 22, Seite 10097-10102
Sprache:
Englisch
DOI:
10.1073/pnas.0914918107
ISSN:
0027-8424;
1091-6490
Entstehung:
Anmerkungen:
Beschreibung:
Telomeres, the protein–DNA complexes at the ends of linear chromosomes, 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 congenita 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 dysfunction and cellular senescence, but maintains its DNA interstrand cross-link repair function in the whole genome. These results identify Apollo as a crucial actor in telomere maintenance in vivo, independent of its function as a general DNA repair factor.