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Mitosis-specific acetylation tunes Ran effector binding for chromosome segregation
Xiaoling Bao1, Heng Liu1, Xing Liu2
1Hefei National Laboratory for Physical Sciences at Microscale, and School of Life Sciences, University of Science and Technology of China, Hefei 230027, China.
Journal of Molecular Cell Biology
|October 18, 2017
Summary
A novel acetylation mechanism regulates the Ran-GTPase pathway, crucial for cell division. TIP60 enzyme modifies Ran, controlling its interaction with Mog1 and RCC1, ensuring accurate chromosome segregation during mitosis.
Area of Science:
- Cell Biology
- Molecular Biology
- Genetics
Background:
- Faithful transmission of genetic information during cell division depends on accurate mitotic spindle assembly and chromosome segregation.
- The Ran GTPase is vital for mitotic spindle assembly, but its regulation by post-translational modifications remains unclear.
Purpose of the Study:
- To elucidate the structural and functional interplay between Ran, Mog1, and RCC1 during mitosis.
- To characterize the role of acetylation in regulating Ran-GTP levels and its impact on chromosome segregation.
Main Methods:
- X-ray crystallography to solve the Ran-Mog1 complex structure.
- Structure-guided functional assays and biochemical characterization.
- Analysis of Ran acetylation by TIP60 and its effect on protein interactions.
Main Results:
- A novel mitosis-specific acetylation-regulated interaction between Ran and Mog1 was identified.
- Mog1 competes with RCC1 for Ran binding, inhibiting GTP loading.
- TIP60-mediated acetylation of Ran (Lys134) liberates Mog1, promoting RCC1 binding and increasing Ran-GTP levels.
- Elevated Ran-GTP is essential for proper chromosome alignment.
Conclusions:
- TIP60-mediated acetylation of Ran provides a homeostatic control mechanism for Ran-GTP levels during mitosis.
- This regulatory pathway fine-tunes Ran effector binding, ensuring accurate chromosome segregation.