Chromatin loops are responsible for higher counts of small DNA fragments induced by high-LET radiation, while chromosomal domains do not affect the fragment sizes

Abstract

Purpose: To apply a polymer model of DNA damage induced by high-LET (linear energy transfer) radiation and determine the influence of chromosomal domains and loops on fragment length distribution.

Materials and methods: The yields of DSB (double-strand breaks) induced by high-LET radiation were calculated using a track structure model along with a polymer model of DNA packed in the cell nucleus. The cell nucleus was constructed to include the chromosomal domains and chromatin loops. The latter were generated by the random walk method.

Results and conclusions: We present data for DSB yields per track per cell, DNA fragment sizes, the radial distribution of DSB with respect to the track center, and the distribution of 0, 1, 2, and more DSB from a single particle. Calculations were carried out for a range of particles including He (40 keV/μm), N (225 keV/μm), and Fe ions (150 keV/μm). Situations relevant to PFGE (pulsed-field gel electrophoresis) and microbeam experiments with direct irradiation of the cell nucleus were simulated to demonstrate the applicability of the model. Data show that chromosomal domains do not have a significant influence on fragment-size distribution, while the presence of DNA loops increases the frequencies of smaller fragments by nearly 30% for fragment sizes in the range from 2 kbp (bp = base pair) to 20 kbp.

Keywords:

• DSB
• DNA fragment
• DNA organization
• chromosomal domain
• chromatin loop
• high-LET ion