At mitosis, a protein called tankyrase 1 serves as protector by separating sister chromatid strands to prevent their telomeres from fusing, conclude Hsiao and Smith.
The team had previously shown that cells lacking tankyrase 1 arrest at mitosis when their sister chromatid telomeres remain associated via protein-protein interactions—even though normal separation occurs along the rest of the chromatid pair. That work highlighted the unique nature of telomere cohesion and led the team to investigate more closely how and why tankyrase 1 prompts telomere separation.
For the how, the team's studies indicate that tankyrase prompts the removal of a telomere-specific TIN2/TRF1 complex that binds to chromatid cohesion proteins. As for the why, the authors demonstrate that promoting sister telomere separation prevents their fusion. After DNA replication, telomeres are processed to generate 3′ overhangs that form protective t loop structures by strand invasion. If chromatid separation does not occur, the DNA ends are at risk of invading the sister strand, and end joining. Indeed, many of the unseparated telomeres in tankyrase-lacking cells were fused together (by nonhomologous end joining). The team would now like to dissect the timing of 3′ end processing and sister telomere separation to understand when tankyrase 1 acts. RW