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Reports

Bin1 Interacts with and Restrains the DNA End-Binding Protein Complex Ku

Arivudainambi Ramalingam, George E. Farmer, Thomas D. Stamato and George C. Prendergast

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The Bin1 gene encodes a BAR adapter protein that suppresses cancer by poorly defined mechanisms. In an effort to gain insights, we identified cellular proteins that formed biochemical complexes with Bin1 protein. Here we report that Bin1 physically binds to Ku, a DNA end-binding protein that functions in telomere maintenance, apoptosis, and DNA repair after genotoxic stress. Both Ku70 and Ku80 were purified from human and murine cell extracts using the Bin1 BAR domain as an affinity matrix. A BAR domain mutation which destroys antioncogenic activity completely abolished Ku binding, supporting functional relevance. To further evaluate its meaning, we investigated interactions between the Bin1 homolog hob1+ and the Ku homologs pku70+ and pku80+ in fission yeast. Notably, deleting pku70+ or pku80+ relieved the survival defect displayed by hob1Δ cells after treatment with the DNA damaging agent phleomycin, suggesting that hob1+ may restrain Ku. Consistent with this notion, telomere length was altered in hob1Δ cells. The potential relevance of Bin1-Ku interaction to cancer are discussed in light of these findings.

Authors

Arivudainambi Ramalingam

Lankenau Institute for Medical Research; Wynnewood, PA USA

George E. Farmer

DuPont Pharmaceuticals Company; Wilmington PA USA

Thomas D. Stamato

Lankenau Institute for Medical Research; Wynnewood PA USA

George C. Prendergast

Lankenau Institute for Medical Research; Wynnewood Pennsylvania USA

Purchase article for $19

Subscribe to this journal for $129/year