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PMID: 11402064 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

HCP-4, a CENP-C-like protein in Caenorhabditis elegans, is required for resolution of sister centromeres.

The Journal of cell biology ·Vol. 153 ·No. 6 ·2001-06-11 ·Pages 1199-208

Moore LL, Roth MB

Abstract

The centromere plays a critical role in the segregation of chromosomes during mitosis. In mammals, sister centromeres are resolved from one another in the G2 phase of the cell cycle. During prophase, chromosomes condense with sister centromeres oriented in a back to back configuration enabling only one chromatid to be captured by each half spindle. To study this process, we identified a centromere protein (CENP)-C-like protein, holocentric protein (HCP)-4, in Caenorhabditis elegans based on sequence identity, loss of function phenotype, and centromeric localization. HCP-4 is found in the cytoplasm during interphase, but is nuclear localized in mitosis, where it localizes specifically to the centromere. The localization of HCP-4 to the centromere is dependent on the centromeric histone HCP-3; in addition, HCP-3 and HCP-4 are both required for localization of a CENP-F-like protein, HCP-1, indicating an ordered assembly pathway. Loss of HCP-4 expression by RNA-mediated interference resulted in a failure to generate resolution of sister centromeres on chromosomes, suggesting that HCP-4 is required for sister centromere resolution. These chromosomes also failed to form a functional kinetochore. Thus, the CENP-C-like protein HCP-4 is essential for both resolution sister centromeres and attachment to the mitotic spindle.

MeSH Terms
Amino Acid Sequence Animals Base Sequence Caenorhabditis elegans/genetics,metabolism,physiology Caenorhabditis elegans Proteins Centromere/physiology Chromosomal Proteins, Non-Histone/genetics DNA, Helminth Helminth Proteins/genetics,metabolism,physiology Humans Kinetochores/metabolism,physiology Mice Molecular Sequence Data Sequence Homology, Amino Acid
Chemicals
Caenorhabditis elegans Proteins Chromosomal Proteins, Non-Histone DNA, Helminth HCP-4 protein, C elegans Helminth Proteins centromere protein C
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Moore L L
Division of Basic Sciences, Molecular and Cellular Biology Program, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA.
Roth M B
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Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
DOI
10.1083/jcb.153.6.1199
Published
2001-06-11
Pages
1199-208
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2192019
Subset
IM
Grants
NIGMS NIH HHS · GM48435 · United States
Databases
GENBANK
AF321299
Corrections
CommentIn
PMID: 11402076
External Links
PubMed source DOI: 10.1083/jcb.153.6.1199 PMC Full Text View journal details
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