DNA double-strand breaks coupled with PARP1 and HNRNPA2B1 binding sites flank coordinately expressed domains in human chromosomes.
oleh: Nickolai A Tchurikov, Olga V Kretova, Daria M Fedoseeva, Dmitri V Sosin, Sergei A Grachev, Marina V Serebraykova, Svetlana A Romanenko, Nadezhda V Vorobieva, Yuri V Kravatsky
| Format: | Article |
|---|---|
| Diterbitkan: | Public Library of Science (PLoS) 2013-04-01 |
Deskripsi
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.