Review: Proximity effects in the production of chromosome aberrations by ionizing radiation

Abstract

Abstract. After ionizing radiation has induced double-strand DNA breaks (dsb), misrejoining produce s chrom osome aberrations. Aberration yields are in¯uenced by`proxim ity' effects, i.e. by the dependence of misrejoining probabilities on initial dsb separations. We survey proxim ity effects, emphasizing implication s for chromosom e aberration-formation mechanisms, for chromatin geometry, and for dose ± response relation s. Evidence for proxim ity effects comes from observed biases for centric rin gs and against three-way interchanges, relative to dicentrics or translocations. Other evidence comes from the way aberration yields depend on radiation dose and quality, tigh tly bunched ionizations being relatively effective. We conclude : (1) that misrejoining probabilities decrease as the distance between dsb at the tim e of their formation increases, and alm ost all misrejoining occurs among dsb initially separated by <1/3 of a cell nucleus diameter; (2) that chromosomes occupy (irregula r) territories during the G 0 /G 1 phase of the cell cycle, having dim ensions also rough ly 1/3 of a cell nucleus diameter; (3) that proxim ity effects have the potential to probe how much differen t chromosomes intertwine or move relative to each other; and (4) that incorporation of proxim ity effects into the classic random breakage-and-reunion model allows quantitative interrelation of yields for many differen t aberration types and of data obtained with various FISH painting methods or whole-genome scorin g.

Nuclear dynamics of radiation-induced foci in euchromatin and heterochromatin

“…This range is in good agreement with the theoretical distances at which two DSBs trigger chromosomal rearrangements [92, 93]. In addition, clustered RIF tend to be more persistent than isolated RIF (Figure 3), suggesting that DSBs associated with RIF clusters are more difficult to repair.…”

Subdiffusion Supports Joining Of Correct Ends During Repair Of DNA Double-Strand Breaks

“…The influence of initial distance between DSB sites on the probability of mis-rejoining is under debate, as well as the possibility of mechanisms bringing DSB sites into closer vicinity during damage processing1. Estimates on break interaction distances based on biophysical modelling vary between 100 nm and several μm234. Simulation models for DNA repair based on normal diffusion of ends tend to overestimate the fraction of unrejoined DSB after long repair times5.…”

Using Chimaeric Expression Sequence Tag as the Reference to Identify Three-Dimensional Chromosome Contacts

“…Especially to the chromosomal translocation-mediated fusion transcripts in tumour cells, the ‘contact-first’ model and the ‘breakage-first’ model have been postulated. 25 Under either scenario, a spatial proximity effect is obvious. 25 Consequently, both chromosomal translocation-mediated and transcription-mediated fusion transcripts can be used to indicate the physical proximities between genes.…”

“…25 Under either scenario, a spatial proximity effect is obvious. 25 Consequently, both chromosomal translocation-mediated and transcription-mediated fusion transcripts can be used to indicate the physical proximities between genes. Through a literature curation, we found that two gene pairs ( RGS17 / TBL1XR1 and BCAS3 / BCAS4 ) identified from the human ESTs libraries have been verified to be spatially proximate by fluorescence in situ hybridization experiments.…”