Figure 6. Model depicting the role of RAP1-SUN1-mediated telomere-nuclear envelope attachment during telomere-telomere recombination in ALT cells. (A) The interaction between RAP1 and SUN1 contributes to telomere anchorage to the nuclear envelope. Unknown kinases might phosphorylate the coil domain of RAP1, inducing RAP1 release from SUN1. Additionally, SUN1 might connect with an unknown telomere-binding protein, and this interaction may provide another telomere-nuclear envelope tethering mechanism to constrain the telomere from freely roaming. The molecular mechanism of how the telomeres depart from the nuclear envelope to the APB remains a mystery. (B) The depletion of SUN1 leads to the release telomeres from the nuclear envelope anchorage and increases the APB formation. However, the RAP1-SUN1 chimera enforces anchorage and decreases the APB formation in ALT cells.