DNA double-strand breaks coupled with PARP1 and HNRNPA2B1 binding sites flank coordinately expressed domains in human chromosomes

• Published in: PLoS genetics Vol. 9; no. 4; p. e1003429
• Main Authors: Tchurikov, Nickolai A, Kretova, Olga V, Fedoseeva, Daria M, Sosin, Dmitri V, Grachev, Sergei A, Serebraykova, Marina V, Romanenko, Svetlana A, Vorobieva, Nadezhda V, Kravatsky, Yuri V
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.04.2013; Public Library of Science (PLoS)
• Subjects: Analysis; Binding Sites; Biology; Cancer; Cell cycle; Chromosome mapping; Chromosome Mapping - methods; Chromosomes; Chromosomes, Human; Deoxyribonucleic acid; DNA; DNA Breaks, Double-Stranded; DNA repair; Experiments; Genes; Genetic regulation; Genetic transcription; Genetics; Genomes; HEK293 Cells; Heterogeneous-Nuclear Ribonucleoprotein Group A-B - genetics; Heterogeneous-Nuclear Ribonucleoprotein Group A-B - metabolism; Humans; Insects; Methods; Observations; Poly (ADP-Ribose) Polymerase-1; Poly(ADP-ribose) Polymerases - genetics; Poly(ADP-ribose) Polymerases - metabolism; Protein Structure, Tertiary; Statistical methods; Russia
• ISSN: 1553-7404; 1553-7390; 1553-7404
• DOI: 10.1371/journal.pgen.1003429

Genome instability plays a key role in multiple biological processes and diseases, including cancer. Genome-wide mapping of DNA double-strand breaks (DSBs) is important for understanding both chromosomal architecture and specific chromosomal regions at DSBs. We developed a method for precise genome-wide mapping of blunt-ended DSBs in human chromosomes, and observed non-random fragmentation and DSB hot spots. These hot spots are scattered along chromosomes and delimit protected 50-250 kb DNA domains. We found that about 30% of the domains (denoted forum domains) possess coordinately expressed genes and that PARP1 and HNRNPA2B1 specifically bind DNA sequences at the forum domain termini. Thus, our data suggest a novel type of gene regulation: a coordinated transcription or silencing of gene clusters delimited by DSB hot spots as well as PARP1 and HNRNPa2B1 binding sites.