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 is present in proliferating cells and has homologs in yeast and human. Mitotic defects in barr embryos become apparent during cycle 16, resulting in a loss of PNS and CNS neurons. Centromeres move apart at the metaphase-anaphase transition and Cyclin B is degraded, but sister chromatids remain connected, resulting in chromatin bridging. This phenotype is similar to that described in TOP2 mutants in yeast. Barren protein localizes to chromatin throughout mitosis. Colocalization and biochemical 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 segregation by facilitating the decatenation of chromatids at anaphase.
Bhat
M A
MA
Howard Hughes Medical Institute, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA.
Philp
A V
AV
Glover
D M
DM
Bellen
H J
HJ
D000705:Anaphase / Q000502:physiology*; D000818:Animals; D018797:Cell Cycle Proteins / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D002455:Cell Division / Q000502:physiology; D002503:Centromere / Q000378:metabolism; D002842:Chromatids / Q000378:metabolism*; D002843:Chromatin / Q000737:chemistry; D002875:Chromosomes / Q000378:metabolism; D003001:Cloning, Molecular; D004250:DNA Topoisomerases, Type II / Q000378:metabolism*; D004330:Drosophila / Q000502:physiology*; D029721:Drosophila Proteins; D004789:Enzyme Activation; D017344:Genes, Insect / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D019476:Insect Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D007814:Larva / Q000737:chemistry / Q000166:cytology / Q000201:enzymology; D008938:Mitosis / Q000502:physiology; D008969:Molecular Sequence Data; D009154:Mutation / Q000502:physiology; D017386:Sequence Homology, Amino Acid; D015003:Yeasts / Q000235:genetics
C103227:Barr protein, Drosophila; D018797:Cell Cycle Proteins; D002843:Chromatin; D029721:Drosophila Proteins; D019476:Insect Proteins; D004250:DNA Topoisomerases, Type II