Remodeling of Telomeres by Telomere Associated Proteins

Univ Of North Carolina Chapel Hill, Chapel Hill NC

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Abstract

[unreadable] DESCRIPTION (provided by applicant): T-loops provide a structural solution to preventing the ends of linear chromosomes from being identified as double strand breaks. This involves the invasion of the 3' single stranded overhang into the proceeding duplex DNA forming a looped telomere structure. T-loops have been isolated and visualized by electron microscopy and can be generated in vitro using the telomere binding protein TRF2 and model telomere templates. The goal of this proposal is to determine how multiprotein telomeric complexes form on model telomeres and identify proteins involved in facilitating or inhibiting t-loop formation. In addition, we will study the role of NBS1 and XRCC3, two proteins involved in homologous recombination and telomere maintenance, for their ability to recognize and remodel telomere structures. We predict that the proteins that interact with TRF2 to form multi-protein complexes in vivo will facilitate and/or prevent the formation of t-loop structures and that NBS1 and XRCC3 may be directly involved in resolving these looped structures producing extrachromosomal telomeric DNA circles similar to those recently observed in cells using the alternative pathway (ALT) for telomere maintenance. [unreadable] [unreadable] [unreadable]