Functional links between <Emphasis Type="Italic">Drosophila</Emphasis> Nipped-B and cohesin in somatic and meiotic cells |
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Authors: | Maria Gause Hayley A Webber Ziva Misulovin Gabe Haller Robert A Rollins Joel C Eissenberg Sharon E Bickel Dale Dorsett |
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Institution: | (1) Edward A. Doisy Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, Saint Louis, MO 63104, USA;(2) Department of Biological Sciences, Dartmouth College, Hanover, NH, USA;(3) Wyeth Research, Pearl River, NY, USA |
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Abstract: | Drosophila Nipped-B is an essential protein that has multiple functions. It facilitates expression of homeobox genes and is also required
for sister chromatid cohesion. Nipped-B is conserved from yeast to man, and its orthologs also play roles in deoxyribonucleic
acid repair and meiosis. Mutation of the human ortholog, Nipped-B-Like (NIPBL), causes Cornelia de Lange syndrome (CdLS),
associated with multiple developmental defects. The Nipped-B protein family is required for the cohesin complex that mediates
sister chromatid cohesion to bind to chromosomes. A key question, therefore, is whether the Nipped-B family regulates gene
expression, meiosis, and development by controlling cohesin. To gain insights into Nipped-B’s functions, we compared the effects
of several Nipped-B mutations on gene expression, sister chromatid cohesion, and meiosis. We also examined association of Nipped-B and cohesin
with somatic and meiotic chromosomes by immunostaining. Missense Nipped-B alleles affecting the same HEAT repeat motifs as CdLS-causing NIPBL mutations have intermediate effects on both gene expression and mitotic chromatid cohesion, linking these two functions and
the role of NIPBL in human development. Nipped-B colocalizes extensively with cohesin on chromosomes in both somatic and meiotic
cells and is present in soluble complexes with cohesin subunits in nuclear extracts. In meiosis, Nipped-B also colocalizes
with the synaptonemal complex and contributes to maintenance of meiotic chromosome cores. These results support the idea that
direct regulation of cohesin function underlies the diverse functions of Nipped-B and its orthologs.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.
Gause, Webber, and Misulovin provided equal contributions. |
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