Molecular basis for CENP-N recognition of CENP-A nucleosome on the human kinetochore

摘要

Dear Editor, Recognition of CENP-A-containing chromatin by CENP-N is a critical step in the assembly of functional kinetochore at the centromere to enable accurate chromosome segregation during cell division [1, 2]. CENP-N is recruited to centromeres during S phase and gradually dissociates during G2 phase. This dynamic assembly of CENP-N onto the centromere is regulated by the change in accessibility to CENP-A’s RG loop (Arg80/Gly81) during the compacting-opening transition of centromeric chromatin structure through the cell cycle[3, 4]. CENP-N has an N-terminal domain that binds to RG loop of CENP-A and a C-terminal domain that interacts with CENP-L to form CENP-N/CENP-L complex (CENP-LN), which further associates with CENP-C and CENP-HIKM to orchestrate kinetochore assembly [1, 3, 5, 6]. Recent studies from hydrogen/deuterium exchange coupled to mass spectrometry (HXMS) have shown that nucleosomal DNA (–21 and –22 nt) had direct contacts with CENP-N in addition to CENP-A’s RG loop [7], suggesting a potential role of CENP-N-DNA interaction in CENP-A nucleosome recognition.