This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Recent studies have highlighted the importance of centromere-specific histone H3-like (CENP-A) proteins in centromere function. We show that Drosophila CID and human CENP-A appear at metaphase as a three-dimensional structure that lacks histone H3. However, blocks of CID/CENP-A and H3 nucleosomes are linearly interspersed on extended chromatin fibers, and CID is close to H3 nucleosomes in polynucleosomal preparations. When CID is depleted by RNAi, it is replaced by H3, demonstrating flexibility of centromeric chromatin organization. Finally, contrary to models proposing that H3 and CID/CENP-A nucleosomes are replicated at different times in S phase, we show that interspersed H3 and CID/CENP-A chromatin are replicated concurrently during S phase in humans and flies. We propose that the unique structural arrangement of CID/CENP-A and H3 nucleosomes presents centromeric chromatin to the poleward face of the condensing mitotic chromosome. This project resulted in the following publication: Blower MD, Sullivan BA, Karpen GH. (2002) Conserved organization of centromeric chromatin in flies and humans. Dev Cell. 2(3): 319-30.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
5P41RR004050-18
Application #
7358048
Study Section
Special Emphasis Panel (ZRG1-CDF-2 (40))
Project Start
2006-05-01
Project End
2007-04-30
Budget Start
2006-05-01
Budget End
2007-04-30
Support Year
18
Fiscal Year
2006
Total Cost
$8,134
Indirect Cost
Name
University of California San Diego
Department
Neurosciences
Type
Schools of Medicine
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093
Funakoshi, Shunsuke; Miki, Kenji; Takaki, Tadashi et al. (2016) Enhanced engraftment, proliferation, and therapeutic potential in heart using optimized human iPSC-derived cardiomyocytes. Sci Rep 6:19111
Rubio-Marrero, Eva N; Vincelli, Gabriele; Jeffries, Cy M et al. (2016) Structural Characterization of the Extracellular Domain of CASPR2 and Insights into Its Association with the Novel Ligand Contactin1. J Biol Chem 291:5788-802
Yin, Xinghua; Kidd, Grahame J; Ohno, Nobuhiko et al. (2016) Proteolipid protein-deficient myelin promotes axonal mitochondrial dysfunction via altered metabolic coupling. J Cell Biol 215:531-542
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Mills, Elizabeth A; Davis, Chung-ha O; Bushong, Eric A et al. (2015) Astrocytes phagocytose focal dystrophies from shortening myelin segments in the optic nerve of Xenopus laevis at metamorphosis. Proc Natl Acad Sci U S A 112:10509-14
Kim, K-Y; Perkins, G A; Shim, M S et al. (2015) DRP1 inhibition rescues retinal ganglion cells and their axons by preserving mitochondrial integrity in a mouse model of glaucoma. Cell Death Dis 6:e1839
Khakh, Baljit S; Sofroniew, Michael V (2015) Diversity of astrocyte functions and phenotypes in neural circuits. Nat Neurosci 18:942-52
Ju, Won-Kyu; Kim, Keun-Young; Noh, You Hyun et al. (2015) Increased mitochondrial fission and volume density by blocking glutamate excitotoxicity protect glaucomatous optic nerve head astrocytes. Glia 63:736-53

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