High LET radiation produces DSBs located non-randomly in the genome: recent data indicate DSB clustering along DNA on kbp-Mbp scales. A DSB cluster on a chromosome is made by one-track action in a stochastic pattern influenced by chromatin geometry and the structure of the track penumbra. This presentation focuses on computer and theoretical analysis of DSB clustering along chromatin in human fibroblasts caused by nitrogen ions, emphasizing large scales, up to the full length of a chromosome. A Monte Carlo numerical model, DNA break, is used to develop a coarse-grained, mechanistic approach. Chromatin is modeled as a random walk on a cubic lattice, and the radiation tracks hitting the chromatin are modeled as straight lines with surrounding penumbras hitting lattice sites. We compared several models of distributions of DSBs in the penumbra. We used the simulated one-track fragmentsize distribution function and the randomly-located-clusters (RLC) formalism to obtain results for high doses (about 100 Gy). The algorithm reproduces nonrandomness in fragment sizes found in current radiation experiments with chromatin on large scales. The RLC formalism was recently cross-checked numerically and by an independent analysis in discrete spaces.

---

Presentation