Chromosome Folding Promotes Intrachromosomal Aberrations under Radiation- and Nuclease-Induced DNA Breakage.

The long-standing question in radiation and cancer biology is how principles of chromosome organization impact the formation of chromosomal aberrations (CAs). To address this issue, we developed a physical modeling approach and analyzed high-throughput genomic data from chromosome conformation capture (Hi-C) and translocation sequencing (HTGTS) methods. Combining modeling of chromosome structure and of chromosomal aberrations induced by ionizing radiation (IR) and nuclease we made predictions which quantitatively correlated with key experimental findings in mouse chromosomes: chromosome contact maps, high frequency of cis-translocation breakpoints far outside of the site of nuclease-induced DNA double-strand breaks (DSBs), the distinct shape of breakpoint distribution in chromosomes with different 3D organizations.

[Biophysical modeling of dose response for γ-ray induced complex chromosomal aberrations].

Experiments with FISH painting of chromosomes, including full-color mFISH, have revealed unexpectedly high yields of complex chromosomal aberrations (CA). The ratio of complex and simple aberrations observed in the 1st postirradiation mitosis has proved to depend on the cell line, LET and time after irradiation in a complicated way. According to the widely accepted viewpoint, interchanges are formed as a result of interaction between either contacting lesions or those having come into contact on a boundary between chromosome territories.

[Radiation induced chromosomal instability: dose response study based on biophysical modeling].

The increased level of non-clonal chromosomal aberrations in the progeny of irradiated cells is recognized as the manifestation of radiation induced chromosomal instability (CI). The shape of the CI dose-response is different from that in the first post-irradiation mitosis; however, the origin of this difference is not established at present experimentally. In the present work, CI dose-response for unstable chromosomal aberrations is studied on the basis of the biophysical model of CI, taking into account formation of delayed dicentrics at different times after irradiation.

[Mechanistic modelling allows to assess pathways of DNA lesion interactions underlying chromosome aberration formation].

The knowledge of radiation-induced chromosomal aberration (CA) mechanisms is required in many fields of radiation genetics, radiation biology, biodosimetry, etc. However, these mechanisms are yet to be quantitatively characterised. One of the reasons is that the relationships between primary lesions of DNA/chromatin/chromosomes and dose-response curves for CA are unknown because the pathways of lesion interactions in an interphase nucleus are currently inaccessible for direct experimental observation.