Separation vs. replication of inactive and active centromeres in neoplastic cells

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.