title: DNA double-strand breaks coupled with PARP1 and HNRNPA2B1 binding sites flank coordinately expressed domains in human chromosomes.
abstract: 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.
authors.affiliation: Department of Genome Organization, Engelhardt Institute of Molecular Biology, Moscow, Russia. tchurikov@eimb.ru
authors.forename: Nickolai A
authors.initials: NA
authors.lastname: Tchurikov
authors.forename: Olga V
authors.initials: OV
authors.lastname: Kretova
authors.forename: Daria M
authors.initials: DM
authors.lastname: Fedoseeva
authors.forename: Dmitri V
authors.initials: DV
authors.lastname: Sosin
authors.forename: Sergei A
authors.initials: SA
authors.lastname: Grachev
authors.forename: Marina V
authors.initials: MV
authors.lastname: Serebraykova
authors.forename: Svetlana A
authors.initials: SA
authors.lastname: Romanenko
authors.forename: Nadezhda V
authors.initials: NV
authors.lastname: Vorobieva
authors.forename: Yuri V
authors.initials: YV
authors.lastname: Kravatsky
mesh_terms: D001665:Binding Sites; D002874:Chromosome Mapping / Q000379:methods*; D002877:Chromosomes, Human; D053903:DNA Breaks, Double-Stranded; D057809:HEK293 Cells; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics* / Q000378:metabolism; D017434:Protein Structure, Tertiary
chemical_list: D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B; C439768:hnRNP A2; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases