Work

Scm3 interacts with the N-terminal tail of Cse4 to regulate kinetochore assembly in budding yeast

Year: 2026

Type: article

Abstract: The kinetochore is a multiprotein complex formed at the centromeres and is essential for the faithful chromosome segregation. In most of the organisms, the kinetochore is assembled on a specialized centromeric nucleosome where histone H3 is replaced by a variant, named CENP-A. In budding yeast, Cse4 (CENP-A in humans) is recruited to the centromeric nucleosome through an interaction between its C-terminal domain and a specific chaperone, Scm3 (HJURP in humans). Interestingly, following Cse4 recruitment during S phase, Scm3 persists and is dynamically exchanged at the centromeres during other stages of the cell cycle. Recent in vitro studies have reported that Scm3 also interacts with N-terminal of Cse4 (N-Cse4), which in turn facilitates a better interaction of Ame1-Okp1 (AO) of COMA subcomplex with N-Cse4, which promotes kinetochore assembly. In this work, using genetic and biochemical assays, we provide in vivo evidence of the interaction between Scm3 and N-Cse4. Additionally, by artificially tethering Scm3, we show that its association has the potential to stabilize a missegregating chromosome with an inactive centromere. We propose that at the centromeres, Scm3 has 2 functions in tandem-Cse4 deposition and stabilization of N-Cse4, which together culminate in proper kinetochore assembly. This work has clinical significance as both CENP-A and HJURP are upregulated under disease states, which can predispose the cells to aneuploidy, a hallmark of cancer cells.

Source: Genetics

DOI: 10.1093/genetics/iyag134