The inactive centromeres in neoplastic and transformed cells exhibit premat
ure separation at prophase or pro-metaphase. The factor(s) that control thi
s behavior are not known. Using a human breast cancer cell line, MDA 435, a
nd a transformed mouse cell line (L929), we studied the relationship betwee
n the sequence of centromere separation and the replication of centromeric
region associated with the active and inactive centromeres. Whereas the ina
ctive centromeres in L929 cells replicate their pericentric heterochromatin
earlier than that associated with the active centromeres, those in MBA 435
cells exhibited no strong correlation between early separation and replica
tion. A comparison between the intragenomic patterns of separation with rep
lication of only active centromeres showed that the former is not dependent
upon the latter in either L929 cells or MDA 435 cells. These studies indic
ate that, whereas inactive centromeres in neoplastic cells separate prematu
rely in different species, there is no uniformity in the control for replic
ation nor does the timing of separation depend upon the timing of replicati
on of the centric region. (C) 2000 Elsevier Science Inc. All rights reserve
d.