Ziel
In eukaryotes the avaliability of the genetic information stored in the DNA is modulated by the interactions of this molecule with a broad spectrum of nuclear proteins such as histones and non-histone proteins. Histones are the main protein components of t he chromatin, where core histones organize DNA into nucleosome core particles and the linker histones bind to the regions contacting adjacent nucleosomes in the chromatin fiber. Although there has recently been a renewed interest in the functional and stru ctural characterization of histone variants, their role in the modulation of chromatin folding and dynamics is poorly understood. Histones H2A and H1 are characteristic for presenting the widest variability of variants among histones, including roles relat ed to DNA double-strand breaks repair, cell cycle checkpoints, and tumor supression. The present project represents a very innovative, high quality and multidisciplinary scientific work whose aim is to develop a molecular and evolutionary analysis of diffe rent core and linker histone proteins. The objetives proposed are: 1) the isolation and characterization of core and linker histone variants in vertebrate and protozoan lineages, 2) the molecular evolutionary analysis of core and linker histone variants to wards their functional diversification related to different chromatin structures, 3) the structural and functional characterization of chromatin complexes reconstituted from core histone variants including H2A.X and H2A.Z and further characterization of th e interactions of linker histones with chromatin. The analysis of such protein structures and the functional consequences of their modes of interaction with DNA will allow us to establish links with mechanisms involved in the altered chromatin conformation s arising from pathological states as cancer.
Wissenschaftliches Gebiet
Aufforderung zur Vorschlagseinreichung
FP6-2004-MOBILITY-6
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