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First published online 5 August 2003
doi: 10.1242/jcs.00682


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Journal of Cell Science 116, 3811-3823 (2003)
doi: 10.1242/jcs.00682


Research Article

Barrier-to-autointegration factor plays crucial roles in cell cycle progression and nuclear organization in Drosophila

Kazuhiro Furukawa1,2,*, Shin Sugiyama4, Shinichi Osouda2, Hidemasa Goto5, Masaki Inagaki5, Tsuneyoshi Horigome3, Saburo Omata1,2, Maeve McConnell6, Paul A. Fisher6 and Yasuyoshi Nishida4

1 Department of Chemistry, Faculty of Science, Niigata University, Niigata 950-2181, Japan
2 Graduate School of Science and Technology, Niigata University, Niigata 950-2181, Japan
3 Center for Instrumental Analysis, Niigata University, Niigata 950-2181, Japan
4 Division of Biological Science, Graduate School of Science, Nagoya University, Nagoya 464-8602, Japan
5 The Laboratory of Biochemistry, Aichi Cancer Center Research Institute, Nagoya 464-8681, Japan
6 Department of Pharmacological Sciences, School of Medicine, University Medical Center, State University of New York at Stony Brook, Stony Brook, New York 11794-8651, USA

* Author for correspondence (e-mail: furukawa{at}chem.sc.niigata-u.ac.jp)

Accepted 23 May 2003

Barrier-to-autointegration factor (BAF) is potentially a DNA-bridging protein, which directly associates with inner nuclear membrane proteins carrying LEM domains. These features point to a key role in regulation of nuclear function and organization, dependent on interactions between the nuclear envelope and chromatin. To understand the functions of BAF in vivo, Drosophila baf null mutants generated by P-element-mediated imprecise excision were analyzed. Homozygous null mutants showed a typical mitotic mutant phenotype: lethality at the larval-pupal transition with small brains and missing imaginal discs. Mitotic figures were decreased but a defined anaphase defect as reported for C. elegans RNAi experiments was not observed in these small brains, suggesting a different phase or phases of cell cycle arrest. Specific abnormalities in interphase nuclear structure were frequently found upon electron microscopic examination of baf null mutants, with partial clumping of chromatin and convolution of nuclear shape. At the light microscopic level, grossly aberrant nuclear lamina structure and B-type lamin distribution correlated well with the loss of detectable amounts of BAF protein from nuclei. Together, these data represent evidence of BAF's anticipated function in mediating interactions between the nuclear envelope and interphase chromosomes. We thus conclude that BAF plays essential roles in nuclear organization and that these BAF functions are required in both M phase and interphase of the cell cycle.

Key words: BAF, Cell cycle, Lamin, Nuclear envelope, Chromosome, Replication


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