Centromeres are essential regions of chromosomes, where the kinetochores assemble. The kinetochores provide the attachment sites for mitotic spindle microtubules for accurate chromosome segregation during cell division. Thus, maintaining centromere identity is vital for genome integrity. The identity of centromeres is epigenetically determined by centromeric histone H3, CENP-A.

Although several factors are known to be critical for CENP-A localization, additional regulatory factors likely exist. In a recent study published online in Cell Research, a research team led by Dr. Zhu Bing from the Institute of Biophysics of the Chinese Academy of Sciences reveals that SENP6 protects the centromere identity by preventing excessive degradation of M18BP1 based on a genome-wide RNAi screen.
SENP6 is essential for the deposition and maintenance of CENP-A at centromeres. Mechanistically, SENP6 is a deSUMOylation enzyme for M18BP1, a known factor regulating CENP-A localization. Upon depletion of SENP6, M18BP1 becomes over-SUMOylated, which promotes its RNF4-dependent polyubiquitination and degradation. Moreover, the same researchers discovered PIAS4 as the specific E3 ligase for M18BP1 SUMOylation.
The study was supported by the Chinese Ministry of Science and Technology of China, the National Natural Science Foundation of China, and the Chinese Academy of Sciences.

SENP6 protects centromere identity by preventing degradation of M18BP1. (Image by Dr. ZHU Bing’s group)

(Reported by Dr. ZHU Bing’s group)