Strand exchange of telomeric DNA catalyzed by the Werner syndrome protein (WRN) is specifically stimulated by TRF2.

Abstract

Werner syndrome (WS), caused by loss of function of the RecQ helicase WRN, is a hereditary disease characterized by premature aging and elevated cancer incidence. WRN has DNA binding, exonuclease, ATPase, helicase and strand annealing activities, suggesting possible roles in recombination-related processes. Evidence indicates that WRN deficiency causes telomeric abnormalities that likely underlie early onset of aging phenotypes in WS. Furthermore, TRF2, a protein essential for telomere protection, interacts with WRN and influences its basic helicase and exonuclease activities. However, these studies provided little insight into WRN's specific function at telomeres. Here, we explored the possibility that WRN and TRF2 cooperate during telomeric recombination processes. Our results indicate that TRF2, through its interactions with both WRN and telomeric DNA, stimulates WRN-mediated strand exchange specifically between telomeric substrates; TRF2's basic domain is particularly important for this stimulation. Although TRF1 binds telomeric DNA with similar affinity, it has minimal effects on WRN-mediated strand exchange of telomeric DNA. Moreover, TRF2 is displaced from telomeric DNA by WRN, independent of its ATPase and helicase activities. Together, these results suggest that TRF2 and WRN act coordinately during telomeric recombination processes, consistent with certain telomeric abnormalities associated with alteration of WRN function.

• Authors: Deanna N Edwards, David K Orren, Amrita Machwe
• Journal: Nucleic acids research (Nucleic Acids Res) Vol. 42 Issue 12 Pg. 7748-61 (Jul 2014) ISSN: 1362-4962 [Electronic] England
• PMID: 24880691 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

Chemical References

• Telomeric Repeat Binding Protein 2
• DNA
• RecQ Helicases

Topics

• Biocatalysis
• DNA (metabolism)
• Protein Structure, Tertiary
• RecQ Helicases (metabolism)
• Telomere (chemistry, metabolism)
• Telomeric Repeat Binding Protein 2 (chemistry, metabolism)