Tankyrase-1 assembly to large protein complexes blocks its telomeric function

Tankyrase-1 poly(ADP-ribosyl)ates the telomere-binding protein TRF1. This post-translational modification dissociates TRF1 from telomeres, enhancing telomerase-mediated telomere elongation. Tankyrase-1 multimerizes via its sterile alpha motif domain, but its functional implication remains elusive. Here, we found that excessive amounts of tankyrase-1 form punctate nuclear foci. This focus formation depends on both homophilic multimerization and heterophilic protein-protein interaction. These foci are functionally dormant because they do not efficiently release TRF1 from telomeres. Consistently, hyper-overexpression of tankyrase-1 attenuates its ability to elongate telomeres. These observations suggest that tankyrase-1 assembly to large protein complexes masks its telomeric function. Structured summary: MINT- 7987689, MINT- 7987677: Tankyrase-1 (uniprotkb:. O95271) and TRF1 (uniprotkb:. P54274) colocalize (MI:. 0403) by fluorescence microscopy (MI:. 0416). MINT- 7987977: Tankyrase-1 (uniprotkb:. O95271) physically interacts (MI:. 0915) with TRF1 (uniprotkb:. P54274) by anti tag coimmunoprecipitation (MI:. 0007). MINT- 7987998: Tankyrase-1 (uniprotkb:. O95271) physically interacts (MI:. 0915) with Tankyrase-1 (uniprotkb:. O95271) by anti tag coimmunoprecipitation (MI:. 0007).