Chromatin organization and DNA damage

Abstract

Genomic DNA is organized three-dimensionally in the nucleus as chromatin. Recent accumulating evidence has demonstrated that chromatin organizes into numerous dynamic domains in higher eukaryotic cells, which act as functional units of the genome. These compacted domains facilitate DNA replication and gene regulation. Undamaged chromatin is critical for healthy cells to function and divide. However, the cellular genome is constantly threatened by many sources of DNA damage (e.g., radiation). How do cells maintain their genome integrity when subjected to DNA damage? This chapter describes how the compact state of chromatin safeguards the genome from radiation damage and chemical attacks. Together with recent genomics data, our finding suggests that DNA compaction, such as chromatin domain formation, plays a critical role in maintaining genome integrity. But does the formation of such domains limit DNA accessibility inside the domain and hinder the recruitment of repair machinery to the damaged site(s) during DNA repair? To approach this issue, we first describe a sensitive imaging method to detect changes in chromatin states in living cells (single-nucleosome imaging/tracking). We then use this method to explain how cells can overcome potential recruiting difficulties; cells can decompact chromatin domains following DNA damage and temporarily increase chromatin motion (∼DNA accessibility) to perform efficient DNA repair. We also speculate on how chromatin compaction affects DNA damage-resistance in the clinical setting.

Keywords: Chromatin domain; Chromatin motion; DNA damage; Damage response; Single-nucleosome imaging.