The chromatin remodeler RSF1 enriched at mitotic centromeres is essential for proper chromosome alignment and segregation and underlying mechanisms remain to be disclosed. We here show that PLK1 recruitment by RSF1 at centromeres creates an activating phosphorylation on Thr236 in the activation loop of Aurora B and this is indispensable for the Aurora B activation. In structural modeling the phosphorylated Thr236 enhances the base catalysis by Asp200 nearby, facilitating the Thr232 autophosphorylation. Accordingly, RSF1-PLK1 is central for Aurora B-mediated microtubule destabilization in error correction. However, under full microtubule-kinetochore attachment RSF1-PLK1 positions at kinetochores, halts activating Aurora B and phosphorylates BubR1, regardless of tension. Spatial movement of RSF1-PLK1 to kinetochores is triggered by Aurora B-mediated phosphorylation of centromeric histone H3 on Ser28. We propose a regulatory RSF1-PLK1 axis that spatiotemporally controls on/off switch on Aurora B. This feedback circuit among RSF1-PLK1-Aurora B may coordinate dynamic microtubule-kinetochore attachment in early mitosis when full tension yet to be generated.
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http://dx.doi.org/10.1038/s41467-021-26220-z | DOI Listing |
Curr Opin Cell Biol
February 2025
Division of Experimental Pathology, Cancer Institute of the Japanese Foundation for Cancer Research (JFCR), Tokyo, Japan; Department of JFCR Cancer Biology, Institute of Science Tokyo, Tokyo, Japan. Electronic address:
Stable transmission of the genome during cell division is crucial for all life forms and is universally achieved by Aurora B-mediated error correction of the kinetochore-microtubule attachments. Aurora B is the enzymatic subunit of the tetrameric protein complex called the chromosomal passenger complex (CPC), and its centromeric enrichment is required for Aurora B to ensure accurate chromosome segregation. How cells enrich the CPC at centromeres is therefore an outstanding question to be elucidated.
View Article and Find Full Text PDFJ Mol Cell Biol
October 2024
School of Biological Sciences, The University of Hong Kong, Kadoorie Biological Sciences Building, Pokfulam Road, Hong Kong, China.
Open Biol
May 2024
Institute of Biochemistry, Justus-Liebig-University Giessen, Giessen, Germany.
Curr Biol
December 2022
Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford, Oxfordshire OX1 3RE, UK. Electronic address:
In eukaryotes, the spindle assembly checkpoint protects genome stability in mitosis by preventing chromosome segregation until incorrect microtubule-kinetochore attachment geometries have been eliminated and chromosome biorientation has been completed. These error correction and checkpoint processes are linked by the conserved Aurora B and MPS1 Ser/Thr kinases. MPS1-dependent checkpoint signaling is believed to be initiated by kinetochores without end-on microtubule attachments, including those generated by Aurora B-mediated error correction.
View Article and Find Full Text PDFJ Mol Cell Biol
September 2022
MOE Key Laboratory for Cellular Dynamics, University of Science and Technology of China School of Life Sciences, Hefei 230027, China.
Error-free mitosis depends on accurate chromosome attachment to spindle microtubules via a fine structure called the centromere that is epigenetically specified by the enrichment of CENP-A nucleosomes. Centromere maintenance during mitosis requires CENP-A-mediated deposition of constitutive centromere-associated network that establishes the inner kinetochore and connects centromeric chromatin to spindle microtubules during mitosis. Although previously proposed to be an adaptor of retinoic acid receptor, here, we show that CENP-R synergizes with CENP-OPQU to regulate kinetochore-microtubule attachment stability and ensure accurate chromosome segregation in mitosis.
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