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- Title
The RepID–CRL4 ubiquitin ligase complex regulates metaphase to anaphase transition via BUB3 degradation.
- Authors
Jang, Sang-Min; Nathans, Jenny F.; Fu, Haiqing; Redon, Christophe E.; Jenkins, Lisa M.; Thakur, Bhushan L.; Pongor, Lőrinc S.; Baris, Adrian M.; Gross, Jacob M.; OʹNeill, Maura J.; Indig, Fred E.; Cappell, Steven D.; Aladjem, Mirit I.
- Abstract
The spindle assembly checkpoint (SAC) prevents premature chromosome segregation by inactivating the anaphase promoting complex/cyclosome (APC/C) until all chromosomes are properly attached to mitotic spindles. Here we identify a role for Cullin–RING ubiquitin ligase complex 4 (CRL4), known for modulating DNA replication, as a crucial mitotic regulator that triggers the termination of the SAC and enables chromosome segregation. CRL4 is recruited to chromatin by the replication origin binding protein RepID/DCAF14/PHIP. During mitosis, CRL4 dissociates from RepID and replaces it with RB Binding Protein 7 (RBBP7), which ubiquitinates the SAC mediator BUB3 to enable mitotic exit. During interphase, BUB3 is protected from CRL4-mediated degradation by associating with promyelocytic leukemia (PML) nuclear bodies, ensuring its availability upon mitotic onset. Deficiencies in RepID, CRL4 or RBBP7 delay mitotic exit, increase genomic instability and enhance sensitivity to paclitaxel, a microtubule stabilizer and anti-tumor drug. The spindle assembly checkpoint (SAC) safeguards chromosome segregation by regulating the anaphase promoting complex/cyclosome (APC/C), allowing chromosomes to correctly attach to mitotic spindles. Here the authors reveal a role for Cullin–RING ubiquitin ligase complex 4 (CRL4) in regulating metaphase to anaphase transition via BUB3 degradation.
- Subjects
SACRAMENTO (Calif.); CHROMOSOME segregation; DNA replication; SPINDLE apparatus; CARRIER proteins; MITOSIS; CHROMOSOMES; UBIQUITIN ligases
- Publication
Nature Communications, 2020, Vol 11, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-019-13808-9