2025-07-10 マックス・プランク研究所(MPI)
Images of chromosome spreads without (left) and with condensation defects (right). © MPI f. Molecular Physiology
<関連情報>
- https://www.mpg.de/25045612/packing-dna-on-time-for-cell-division
- https://www.sciencedirect.com/science/article/pii/S109727652500543X
M18BP1によるコンデンシンIIの活性化 Condensin II activation by M18BP1
Alessandro Borsellini, Duccio Conti, Erin E. Cutts, Rebecca J. Harris, Kai Walstein, Andrea Graziadei, Valentina Cecatiello, Tom F. Aarts, Ren Xie, Abdelghani Mazouzi, Sushweta Sen, Claire Hoencamp, Richard Pleuger, Sabrina Ghetti, Lina Oberste-Lehn, Dongqing Pan, Tanja Bange, Judith H.I. Haarhuis, Anastassis Perrakis, Thijn R. Brummelkamp…Alessandro Vannini
Molecular Cell Available online: 3 July 2025
DOI:https://doi.org/10.1016/j.molcel.2025.06.014
Highlights
- M18BP1 is crucial for condensin II activity in human cells
- Condensin II’s CAP-G2 subunit directly interacts with M18BP1
- MCPH1 competes with M18BP1 and inhibits condensin II activity during interphase
- Phosphorylation drives a switch in binding at mitotic onset, activating condensin II
Summary
Condensin I and II promote the drastic spatial rearrangement of the human genome upon mitotic entry. While condensin II is known to initiate this process in early mitosis, what triggers its activation and loading onto chromatin at this juncture remains unclear. Through genetic and proteomic approaches, we identify MIS18-binding protein 1 (M18BP1), a protein required to maintain centromere identity, as the elusive factor required for condensin II localization to chromatin. M18BP1 directly binds condensin II’s CAP-G2 subunit. The condensin II antagonist MCPH1 also binds to CAP-G2 and outcompetes M18BP1 during interphase to maintain the genome in its uncondensed state. A switch from MCPH1 to M18BP1 at mitotic onset activates condensin II, thus promoting proper chromosome condensation. Regulation of this M18BP1-condensin interaction thus determines both the uncondensed state of the interphase genome and its compacted state in mitosis.
