Requirement of DDX39 DEAD box RNA helicase for genome integrity and telomere protection

Hyun Hee Yoo, In Kwon Chung

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

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 FXLXP 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.

Original languageEnglish
Pages (from-to)557-571
Number of pages15
JournalAging Cell
Volume10
Issue number4
DOIs
Publication statusPublished - 2011 Aug 1

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DEAD-box RNA Helicases
Telomere
Genome
Telomerase
DNA Damage
Telomeric Repeat Binding Protein 2
Chromosomes
Telomere Homeostasis
Telomere Shortening
Chromatids
Cell Nucleus Active Transport
DNA
Human Chromosomes
Metaphase
Small Interfering RNA
Proteins
Maintenance
Amino Acids
Messenger RNA

All Science Journal Classification (ASJC) codes

  • Cell Biology
  • Ageing

Cite this

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abstract = "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 FXLXP 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.",
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Requirement of DDX39 DEAD box RNA helicase for genome integrity and telomere protection. / Yoo, Hyun Hee; Chung, In Kwon.

In: Aging Cell, Vol. 10, No. 4, 01.08.2011, p. 557-571.

Research output: Contribution to journalArticle

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