CHROMATID SEGREGATION AT ANAPHASE REQUIRES THE BARREN PRODUCT, A NOVEL CHROMOSOME-ASSOCIATED PROTEIN THAT INTERACTS WITH TOPOISOMERASE-II

We have isolated a Drosophila gene, barren (barr), required for sister -chromatid segregation in mitosis. barr encodes a novel protein that i s present in proliferating cells and has homologs in yeast and human. Mitotic defects in barr embryos become apparent during cycle 16, resul ting in a loss of PNS and CNS neurons. Centromeres move apart at the m etaphase-anaphase transition and Cyclin B is degraded, but sister chro matids remain connected, resulting in chromatin bridging. This phenoty pe is similar to that described in TOP2 mutants in yeast. Barren prote in localizes to chromatin throughout mitosis. Colocalization and bioch emical experiments indicate that Barren associates with Topoisomerase II throughout mitosis and alters the activity of Topoisomerase II. We propose that this association is required for proper chromosomal segre gation by facilitating the decatenation of chromatids at anaphase.