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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Binding Sites
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Chromosome Mapping / methods*
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Chromosomes, Human*
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DNA Breaks, Double-Stranded*
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HEK293 Cells
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Heterogeneous-Nuclear Ribonucleoprotein Group A-B / genetics*
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Heterogeneous-Nuclear Ribonucleoprotein Group A-B / metabolism
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Humans
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Poly (ADP-Ribose) Polymerase-1
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Poly(ADP-ribose) Polymerases / genetics*
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Poly(ADP-ribose) Polymerases / metabolism
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Protein Structure, Tertiary
Substances
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Heterogeneous-Nuclear Ribonucleoprotein Group A-B
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hnRNP A2
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PARP1 protein, human
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Poly (ADP-Ribose) Polymerase-1
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Poly(ADP-ribose) Polymerases
Grants and funding
This work was supported by grants from the Russian Foundation for Basic Research (#11-04-00091-a, #12-04-01416-a, and #12-04-01311-a) and the Russian Ministry of Education and Science (Agreement #8300). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.