[Globular model of interphase chromosome and intrachromosomal exchange aberrations]

A globular folding model formerly proposed for large-scale interphase chromatin/chromosome organization is investigated here by computer simulation. Large-scale structure of interphase chromosome is suggested to be determined by volumetric interactions between chromosome subunits resulting in folding of subunit chain in a globular state. Structure unit of interphase chromosome is considered as a spherical structure consisting of a cluster of compact chromatin domains. These structure units/domain clusters were termed as a superdomains to emphasize their supradomain organization. Globular state of superdomain chain with excluded volume as well as phase transitions between condensed (globular) and decondensed (coiled) states are studied by dynamic Monte-Carlo approach. Globular model is supported by confocal microscopy data. It extends current view on interphase chromosome as a random Gauss polymer chain. Radiation-induced intrachromosome exchange aberrations (intrachanges) are modeled on the basis of the contact hypothesis. It implies that intrachanges result from radiation damage of chromatin mainly in contacted subunits. Computer modeling of chromosome structure provides a wealth of information about proximity effects and results in prediction of pattern of intrachromosome contacts. Calculated intrachange frequencies agree well with experimental data. Globular model suggests a physical mechanism for conformational changes of large-scale chromosome structure similar to phase transitions in polymer systems. These rearrangements of structure organization of chromosomes in the nuclei following irradiation could be mechanistically linked to the complex chromosome aberrations formation as well as to alteration of gene expression due to position variegation effect.