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

Autor: 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
Jazyk: angličtina
Rok vydání: 2013
Předmět:
Zdroj: PLoS Genetics, Vol 9, Iss 4, p e1003429 (2013)
Druh dokumentu: article
ISSN: 1553-7390
1553-7404
DOI: 10.1371/journal.pgen.1003429
Popis: 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.
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