CenHFDCProject reference: 299986
Funded under :
A novel role for histone chaperones in the dynamics of non-conventional substrates, the CENP-T/-W, complex at the centromere
Total cost:EUR 201 932,4
EU contribution:EUR 201 932,4
Topic(s):FP7-PEOPLE-2011-IEF - Marie-Curie Action: "Intra-European fellowships for career development"
Call for proposal:FP7-PEOPLE-2011-IEFSee other projects for this call
Funding scheme:MC-IEF - Intra-European Fellowships (IEF)
Two essential phases exist in centromere assembly and maturation during the cell cycle; a G1 phase in which CENP-A is replenished to establish replication competent centromeres and a late-S/G2 phase, in which additional assembly events establish a centromeric substrate competent for kinetochore assembly. The centromere provides a unique context in which to examine the question of epigenetic inheritance. Centromere protein A (CENP-A) is a conserved histone H3 variant that replaces canonical H3 specifically at centromeres in all known eukaryotes. CENP-A, which is manufactured in one cell cycle does not assemble into the centromere until passage through mitosis into telophase of the subsequent cell cycle (Jansen et al., 2007), dependent on a unique factor, HJURP, for deposition and maintenance (Dunleavy et al., 2009; Foltz et al., 2009). A histone H3-associated histone fold complex of the centromere, the CENP-T/W complex, assembles specifically through a dynamic exchange mechanism in late S-Phase and G2 (Prendergast et al., 2011). The CENP-T/-W complex is necessary for successful mitosis (Hori et al., 2008; Prendergast et al., 2011). We hypothesise that assembly factors are involved in the loading of the CENP-T/-W complex to the centromere during S-Phase. To investigate this we have purified soluble pre-deposition CENP-W complexes. Several proteins identified as CENP-W interactors by mass spectrometry, including the FACT complex (SSRP1 / Spt16), have previously been reported as histone chaperones. We hypothesize that one (or more) of these candidates plays a role in the post-replicative preparation of centromeric chromatin for kinetochore assembly, through handling unconventional substrates, the CENP-T/-W complex.
EU contribution: EUR 201 932,4
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