3D-structured illumination microscopy reveals clustered DNA double-strand break formation in widespread γH2AX foci after high LET heavy-ion particle radiation

Yoshihiko Hagiwara, Atsuko Niimi, Mayu Isono, Motohiro Yamauchi, Takaaki Yasuhara, Siripan Limsirichaikul, Takahiro Oike, Hiro Sato, Kathryn D. Held, Takashi Nakano, Atsushi Shibata

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

DNA double-strand breaks (DSBs) induced by ionising radiation are considered the major cause of genotoxic mutations and cell death. While DSBs are dispersed throughout chromatin after X-rays or γ-irradiation, multiple types of DNA damage including DSBs, single-strand breaks and base damage can be generated within 1-2 helical DNA turns, defined as a complex DNA lesion, after high Linear Energy Transfer (LET) particle irradiation. In addition to the formation of complex DNA lesions, recent evidence suggests that multiple DSBs can be closely generated along the tracks of high LET particle irradiation. Herein, by using three dimensional (3D)-structured illumination microscopy, we identified the formation of 3D widespread γH2AX foci after high LET carbon-ion irradiation. The large γH2AX foci in G2-phase cells encompassed multiple foci of replication protein A (RPA), a marker of DSBs undergoing resection during homologous recombination. Furthermore, we demonstrated by 3D analysis that the distance between two individual RPA foci within γH2AX foci was approximately 700 nm. Together, our findings suggest that high LET heavy-ion particles induce clustered DSB formation on a scale of approximately 1 μm3. These closely localised DSBs are considered to be a risk for the formation of chromosomal rearrangement after heavy-ion irradiation.

Original languageEnglish
Pages (from-to)109370-109381
Number of pages12
JournalOncotarget
Volume8
Issue number65
DOIs
Publication statusPublished - 2017

All Science Journal Classification (ASJC) codes

  • Oncology

Fingerprint Dive into the research topics of '3D-structured illumination microscopy reveals clustered DNA double-strand break formation in widespread γH2AX foci after high LET heavy-ion particle radiation'. Together they form a unique fingerprint.

  • Cite this

    Hagiwara, Y., Niimi, A., Isono, M., Yamauchi, M., Yasuhara, T., Limsirichaikul, S., Oike, T., Sato, H., Held, K. D., Nakano, T., & Shibata, A. (2017). 3D-structured illumination microscopy reveals clustered DNA double-strand break formation in widespread γH2AX foci after high LET heavy-ion particle radiation. Oncotarget, 8(65), 109370-109381. https://doi.org/10.18632/oncotarget.22679