Developmental Cell: CENP-A Ubiquitylation Is Required for CENP-A Deposition at the Centromere
YoheiNiikura1, RisaKitagawa1, KatsumiKitagawa1
Main Text
CENP-A is a centromere-specific histone variant that determines centromere identity, but how it localizes to centromeres is not completely understood. Previously, we demonstrated that CENP-A deposition at the centromere requires ubiquitylation on lysine 124 (K124) mediated by the CUL4A-RBX1-COPS8 E3 ligase (Niikura et al., 2015). A K124R mutation reduced interaction with HJURP (a CENP-A-specific histone chaperone) and abrogated centromeric localization, but the addition of a mono-ubiquitin at the C terminus of CENP-A K124R restored interaction with HJURP and centromeric localization (Niikura et al., 2015), indicating that “signaling” ubiquitylation is required for CENP-A deposition at centromeres. We also showed that the CUL4A-RBX1 complex is required for loading newly synthesized CENP-A and maintaining preassembled CENP-A at centromeres by using the SNAP-tagged CENP-A system (Niikura et al., 2015). Recently, we found that pre-existing ubiquitylated CENP-A is necessary for the recruitment of newly synthesized CENP-A to the centromere and that CENP-A ubiquitylation is inherited through dimerization during cell division (Niikura et al., 2016). Furthermore, overexpression of mono-ubiquitylated CENP-A creates ectopic functional centromeres (neocentromeres) and causes HJURP accumulation at non-centromeric regions (Niikura et al., 2016). Thus, we proposed that CENP-A ubiquitylation determines centromere location through dimerization (Niikura et al., 2016).
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