The nuclear import of histones is mediated by karyopherins/importins
and specific nucleo-cytoplasmic shuttling-chromatin assembly
factors.
Nima Mosammaparast, Courtney Ewart, Sarah Wilkinson,
Lucy Pemberton
Center for Cell Signaling, University of
Virginia, Box 800577 HSC, Charlottesville, VA 22908, USA
The cell-cycle regulated synthesis and nuclear import of core histones is a
prerequisite to the assembly of histones onto DNA to form chromatin. The
correct assembly of nucleosomes is critical for maintaining genomic
stability in all eukaryotic cells. We show that the nuclear import of
core histone heteromers (H2A and H2B, and H3 and H4) is mediated by a
network of overlapping karyopherins (Kaps)/importins. Within this
network, specific Kaps function as primary import receptors for each
pair. Analysis of the nuclear localization signals (NLSs) within
histones reveals that each contains an amino terminal NLS. Biochemical
isolation of histone-Kap complexes has revealed the presence of
additional proteins that may function as specific transport co-factors.
A complex of H2A, H2B, their primary import Kap, Kap114p, and the
nucleosome assembly protein Nap1p was detected in cytosolic extracts. We
are currently investigating the role of Nap1p in the import of H2A and
H2B. In higher eukaryotes, Nap1 specifically enters the nucleus in S
phase, correlating with the timing of histone synthesis and DNA
replication. In yeast, we can show that Nap1p shuttles between the
nucleus and cytoplasm. Nap1p can interact directly with Kap114p, and
with H2A and H2B, and may serve to bridge the Kap-histone interaction.
Nap1p, however, prevents the association of other Kaps with H2A and H2B.
These data suggest a novel role for Nap1p in the Kap114p-mediated
nuclear import pathway of H2A and H2B.
Return to YGM 2002 Home at SGD