title: Hot spots of DNA double-strand breaks in human rDNA units are produced in vivo.
abstract: Endogenous hot spots of DNA double-strand breaks (DSBs) are tightly linked with transcription patterns and cancer genomics(1,2). There are nine hot spots of DSBs located in human rDNA units(3-6). 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.
authors.affiliation: Department of Epigenetic Mechanisms of Gene Expression Regulation, Engelhardt Institute of Molecular Biology, Moscow, 119334, Russia.
authors.forename: Nickolai A
authors.initials: NA
authors.lastname: Tchurikov
authors.affiliation: Department of Genomic Diversity and Evolution, Institute of Molecular and Cellular Biology SB RAS, Lavrentiev Ave. 8/2, Novosibirsk, 630090, Russia.|Department of Medicine, Novosibirsk State University, Pirogova str. 2, Novosibirsk 630090, Russia.
authors.forename: Dmitry V
authors.initials: DV
authors.lastname: Yudkin
authors.affiliation: Department of Epigenetic Mechanisms of Gene Expression Regulation, Engelhardt Institute of Molecular Biology, Moscow, 119334, Russia.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Gorbacheva
authors.affiliation: Department of Genomic Diversity and Evolution, Institute of Molecular and Cellular Biology SB RAS, Lavrentiev Ave. 8/2, Novosibirsk, 630090, Russia.
authors.forename: Anastasia I
authors.initials: AI
authors.lastname: Kulemzina
authors.affiliation: Department of Natural Science, Novosibirsk State University, Pirogova str. 2, Novosibirsk 630090, Russia.
authors.forename: Irina V
authors.initials: IV
authors.lastname: Grischenko
authors.affiliation: Department of Epigenetic Mechanisms of Gene Expression Regulation, Engelhardt Institute of Molecular Biology, Moscow, 119334, Russia.
authors.forename: Daria M
authors.initials: DM
authors.lastname: Fedoseeva
authors.affiliation: Department of Epigenetic Mechanisms of Gene Expression Regulation, Engelhardt Institute of Molecular Biology, Moscow, 119334, Russia.
authors.forename: Dmitri V
authors.initials: DV
authors.lastname: Sosin
authors.affiliation: Department of Epigenetic Mechanisms of Gene Expression Regulation, Engelhardt Institute of Molecular Biology, Moscow, 119334, Russia.
authors.forename: Yuri V
authors.initials: YV
authors.lastname: Kravatsky
authors.affiliation: Department of Epigenetic Mechanisms of Gene Expression Regulation, Engelhardt Institute of Molecular Biology, Moscow, 119334, Russia.
authors.forename: Olga V
authors.initials: OV
authors.lastname: Kretova
mesh_terms: D002460:Cell Line; D002466:Cell Nucleolus / Q000235:genetics / Q000378:metabolism; D053903:DNA Breaks, Double-Stranded; D004275:DNA, Ribosomal / Q000235:genetics*; D044127:Epigenesis, Genetic; D057809:HEK293 Cells; D006657:Histones / Q000378:metabolism; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D019169:Jurkat Cells; D035463:Pol1 Transcription Initiation Complex Proteins / Q000378:metabolism
chemical_list: D004275:DNA, Ribosomal; C468783:H2AX protein, human; D006657:Histones; D035463:Pol1 Transcription Initiation Complex Proteins; C063844:transcription factor UBF