Compacted chromatin found to be highly resistant to radiation and/or chemical agent damage

Osaka University. Japan: Under the leadership of TAKATA Hideaki (Assistant Professor, Graduate School of Engineering, Osaka University) and MAESHIMA Kazuhiro (Professor, National Institute of Genetics), a group of researchers developed a novel 'solid-phase' system for gentle chromatin manipulation and sensitive DNA damage detection and demonstrate that chromatin compaction protects genomic DNA from radiation damage.
Interestingly, the frequency of γ-ray- or heavy ioninduced DSBs in the compact chromatin was 5–50-fold lower than that in the decondensed chromatin. In addition, the genomic DNA compaction protects against attack by chemical agents. These findings suggest a clear advantage of the compact chromatin domains in maintaining genomic integrity. This group’s discovery also provide a theoretical basis for various novel combinations of cancer therapies.

Abstract

Genomic DNA is three-dimensionally organized into the nucleus, and is thought to form compact chromatin domains. Although chromatin compaction is known to be essential for mitosis, whether it confers other advantages, particularly in interphase cells, remains unknown. Here, we report that chromatin compaction protects genomic DNA from radiation damage. Using a newly developed solid-phase system, we found that the frequency of double-strand breaks (DSBs) in compact chromatin after ionizing irradiation was 5-50-fold lower than in decondensed chromatin. Since radical scavengers inhibited DSB induction in the decondensed chromatin, the condensed chromatin had a lower level of reactive radical generation after ionizing irradiation. We show that chromatin compaction also protects DNA from attack by chemical agents. Our findings suggest that genomic DNA compaction plays an important role in maintaining genomic integrity.