Tankyrase activity is essential for asymmetric division and chromosome segregation in oocyte meiosis

Tankyrase (TNKS) is a poly ADP-ribose polymerase which is known to regulate DNA repair, GLUT4-related vesicles transportation, and mitotic sister telomeres resolution.

In the present study, we reported the novel roles of TNKS in oocyte meiosis.

Using specific chemical inhibitors, Western blot, immunofluorescence staining, mass spectrometry, co-immunoprecipitation, and siRNA interference, we disturbed TNKS activity or depleted TNKS expression to investigate the underlying mechanisms.

Our results showed that TNKS associated with microtubules, and upon loss of TNKS activity, unique phenotypes were observed in oocytes where symmetric division and improper chromosome segregation occurred simultaneously during meiotic maturation. Mass spectrometry data indicated interactions between TNKS and proteins involved in actin filaments, microtubule organization, and cell cycle. Further analysis revealed that TNKS strikingly regulated actin filaments for chromosome-spindle complex motility and cortical polarity establishment through Formin2 and Ran/N-WASP/ARP2 pathways, which are crucial for meiotic asymmetric division. Additionally, we found that TNKS associated with p-PLK1 and affected K40 acetylation of α-Tubulin, and it also regulated BubR1 transportation to kinetochore and synthesis or activity of MPF/Securin, all of which contributed to the formation of meiotic bipolar spindle and precise chromosome separation associated with the cell cycle.

Taken together, our results suggested that poly ADP-ribose polymerase TNKS was required for actin dynamics and cell cycle, which contributed to both asymmetric division and proper chromosome segregation in mouse oocytes.