The probability of double-strand breaks in giant DNA decreases markedly as the DNA concentration increases

TL;DR

This study investigates how the probability of double-strand breaks in giant DNA decreases with increasing DNA concentration, revealing a nearly inverse proportionality and emphasizing the importance of DNA's physical properties.

Contribution

It introduces a new quantitative analysis of DSBs in giant DNA, demonstrating the inverse relationship between DSB probability and DNA concentration and proposing a model based on DNA's semiflexible polymer nature.

Findings

P1 is nearly inversely proportional to DNA concentration above a threshold

A simple model explains the decrease considering DNA as a semiflexible polymer

Single-molecule observation method effectively measures DSBs in giant DNA

Abstract

DNA double-strand breaks (DSBs) represent a serious source of damage for all living things and thus there have been many quantitative studies of DSBs both in vivo and in vitro. Despite this fact, the processes that lead to their production have not yet been clearly understood, and there is no established theory that can account for the statistics of their production, in particular, the number of DSBs per base pair per unit Gy, here denoted by P1, which is the most important parameter for evaluating the degree of risk posed by DSBs. Here, using the single-molecule observation method with giant DNA molecules (166 kbp), we evaluate the number of DSBs caused by gamma-ray irradiation. We find that P1 is nearly inversely proportional to the DNA concentration above a certain threshold DNA concentration. A simple model that accounts for the marked decrease of P1 shows that it is necessary to consider the characteristics of giant DNA molecules as semiflexible polymers to interpret the intrinsic mechanism of DSBs.