Open AccessRequirement of DDX39 DEAD box RNA helicase for genome integrity and telomere protection
Author(s) -
Yoo Hyun Hee,
Chung In Kwon
Publication year - 2011
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1111/j.1474-9726.2011.00696.x
Subject(s) - telomere , shelterin , biology , telomerase , telomere binding protein , helicase , microbiology and biotechnology , rna helicase a , rna , dna , genetics , gene , dna binding protein , transcription factor
Summary Human chromosome ends associate with shelterin, a six‐protein complex that protects telomeric DNA from being recognized as sites of DNA damage. The shelterin subunit TRF2 has been implicated in the protection of chromosome ends by facilitating their organization into the protective capping structure and by associating with several accessory proteins involved in various DNA transactions. Here we describe the characterization of DDX39 DEAD‐box RNA helicase as a novel TRF2‐interacting protein. DDX39 directly interacts with the telomeric repeat binding factor homology domain of TRF2 via the F X L X P motif (where X is any amino acid). DDX39 is also found in association with catalytically competent telomerase in cell lysates through an interaction with hTERT but has no effect on telomerase activity. Whereas overexpression of DDX39 in telomerase‐positive human cancer cells led to progressive telomere elongation, depletion of endogenous DDX39 by small hairpin RNA (shRNA) resulted in telomere shortening. Furthermore, depletion of DDX39 induced DNA‐damage response foci at internal genome as well as telomeres as evidenced by telomere dysfunction‐induced foci. Some of the metaphase chromosomes showed no telomeric signal at chromatid ends, suggesting an aberrant telomere structure. Our findings suggest that DDX39, in addition to its role in mRNA splicing and nuclear export, is required for global genome integrity as well as telomere protection and represents a new pathway for telomere maintenance by modulating telomere length homeostasis.