Visualization of H2AX foci caused by heavy ion particle traversal; Distribution between core track versus non-track damage

Nakajima, Nakako*; Brunton, H.*; Watanabe, Ritsuko; Shrikhande, A.*; Hirayama, Ryoichi*; Matsufuji, Naruhiro*; Fujimori, Akira*; Murakami, Takeshi*; Okayasu, Ryuichi*; Jeggo, P.*; Shibata, Atsushi*

Heavy particle irradiation can produce complex DNA double strand breaks (DSBs) within the particle trajectory. Additionally, secondary electrons, termed delta-electrons, can create low linear energy transfer (LET) damage distant from the track. Using imaging with deconvolution, we show that at 8 hours after exposure to Fe ions, H2AX foci forming at DSBs within the particle track are large and encompass multiple smaller and closely localised foci, which we designate as clustered H2AX foci. We also identified simple H2AX foci distant from the track. They are rapidly repaired. Clustered H2AX foci induced by heavy particle radiation cause prolonged checkpoint arrest compared to simple H2AX foci. However, mitotic entry was observed when 10 clustered foci remain. Thus, cells can progress into mitosis with multiple clusters of DSBs following the traversal of a heavy particle.