The cell cycle is modulated by ubiquitin ligases, including CRL4, which facilitate degradation of the chromatin-bound substrates involved in DNA replication and chromosome segregation. One of the members of the CRL4 complex, RepID (DCAF14/PHIP), recognizes kinetochore-localizing BUB3, known as the CRL4 substrate, and recruits CRL4 to the chromatin/chromosome using the WD40 domain. Here, we show that the RepID WD40 domain provides different platforms to CRL4 and BUB3. Deletion of the H-box or exon 8 located in the RepID WD40 domain compromises the interaction between RepID and CRL4, whereas BUB3 interacts with the exon 1-2 region. Moreover, deletion mutants of other exons in the WD40 domain lost chromatin binding affinity. Structure prediction revealed that the RepID WD40 domain has two beta-propeller folds, linked by loops, which are possibly crucial for chromatin binding. These findings provide mechanistic insights into the space occupancy of the RepID WD40 domain to form a complex with CRL4, BUB3, or chromatin.
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| http://dx.doi.org/10.1016/j.bbrc.2021.06.047 | DOI Listing |
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