Hot spots of DNA double-strand breaks in human rDNA units are produced in vivo

• DOI: 10.1038/srep25866
• Publication Date: 2016-05-10T09:41:14Z
• Authors: Nickolai A. Tchur...; Dmitry V. Yudkin; Maria A. Gorbacheva; Anastasia I. Kule...; Irina V. Grischenko; Daria M. Fedoseeva; Dmitri V. Sosin; Yuri V. Kravatsky; Olga V. Kretova
• Keywords: 0303 health sciences; DNA, Ribosomal; Article; Cell Line; Epigenesis, Genetic; Histones; Jurkat Cells; 03 medical and health sciences; HEK293 Cells; Humans; DNA Breaks, Double-Stranded; Pol1 Transcription Initiation Complex Proteins; Cell Nucleolus; In Situ Hybridization, Fluorescence

AbstractEndogenous hot spots of DNA double-strand breaks (DSBs) are tightly linked with transcription patterns and cancer genomics1,2. There are nine hot spots of DSBs located in human rDNA units3–6. Here we describe that the profiles of these hot spots coincide with the profiles of γ-H2AX or H2AX, strongly suggesting a high level of in vivo breakage inside rDNA genes. The data were confirmed by microscopic observation of the largest γ-H2AX foci inside nucleoli in interphase chromosomes. In metaphase chromosomes, we observed that only some portion of rDNA clusters possess γ-H2AX foci and that all γ-H2AX foci co-localize with UBF-1 binding sites, which strongly suggests that only active rDNA units possess the hot spots of DSBs. Both γ-H2AX and UBF-1 are epigenetically inherited and thus indicate the rDNA units that were active in the previous cell cycle. These results have implications for diverse fields, including epigenetics and cancer genomics.