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Papers In Press, published online ahead of print November 1, 2001
Department of Microbiology, University of Virginia, Charlottesville, VA 22908
Corresponding Author: lfp2n{at}virginia.edu
The correct assembly of chromatin is necessary for the maintenance of genomic stability in eukaryotic cells. A critical step in the assembly of new chromatin is the cell-cycle regulated synthesis and nuclear import of core histones. Here we demonstrate that the nuclear import pathway of histone H3 and H4 is mediated by at least two karyopherins/importins, Kap123p and Kap121p. Cytosolic H4 is found associated with Kap123p and H3. Kap121p is also present in the H4-PrA associated fractions, albeit in lesser amounts than Kap123p, suggesting that this Kap serves as an additional import receptor. We further demonstrate that cytosolic Kap123p is associated with acetylated H3 and acetylated H4. H3 and H4 each contain a nuclear localization signal (NLS) in their amino-terminal domains. These amino-terminal domains were found to be essential for the nuclear accumulation of H3 and H4-GFP reporters. Each NLS mediated direct binding to Kap123p and Kap121p, and decreased nuclear accumulation of H3 and H4 NLS-GFP reporters was observed in specific kap mutant strains. H3 and H4 are the first histones to be assembled onto DNA, and these results show that their import is mediated by at least two import pathways.
J. Biol. Chem, 10.1074/jbc.M106845200
Submitted on July 19, 2001
Revised on November 1, 2001
Accepted on November 1, 2001
Pathways mediating the nuclear import of histone H3 and H4 in yeast
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