DNA Double-Strand Breaks Coupled with PARP1 and HNRNPA2B1 Binding Sites Flank Coordinately Expressed Domains in Human Chromosomes

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. © 2013 tchurikov et al.