Mis16 and Mis18 are subunits of a protein complex required for incorporation of 
the histone H3 variant CenH3 (Cnp1/CENP-A) into centromeric chromatin in 
Schizosaccharomyces pombe and mammals. How the Mis16-Mis18 complex performs this 
function is unknown. Here, we report that the Mis16-Mis18 complex is required 
for centromere localization of Scm3(Sp), a Cnp1-binding protein related to 
Saccharomyces cerevisiae Scm3. Scm3(Sp) is required for centromeric localization 
of Cnp1, while Scm3(Sp) localizes at centromeres independently of Cnp1. Like the 
Mis16-Mis18 complex but unlike Cnp1, Scm3(Sp) dissociates from centromeres 
during mitosis. Inactivation of Scm3(Sp) or Mis18 increases centromere 
localization of histones H3 and H2A/H2B, which are largely absent from 
centromeres in wild-type cells. Whereas S. cerevisiae Scm3 is proposed to 
replace histone H2A/H2B in centromeric nucleosomes, the dynamic behavior of S. 
pombe Scm3 suggests that it acts as a Cnp1 assembly/maintenance factor that 
directly mediates the stable deposition of Cnp1 into centromeric chromatin.