Ribonucleoprotein-masked nicks at 50-kbp intervals in the eukaryotic genomic DNA
By using a microscopic approach, field inversion single-cell gel electrophoresis, we show that preformed single-strand discontinuities are present in the chromatin of resting and proliferating mammalian and yeast cells. These single-strand breaks are primarily nicks positioned at [almost equal to]50...
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creator | Székvölgyi, Lóránt Rákosy, Zsuzsa Bálint, Bálint L Kókai, Endre Imre, László Vereb, György Bacsó, Zsolt Goda, Katalin Varga, Sándor Balázs, Margit Dombrádi, Viktor Nagy, László Szabó, Gábor |
description | By using a microscopic approach, field inversion single-cell gel electrophoresis, we show that preformed single-strand discontinuities are present in the chromatin of resting and proliferating mammalian and yeast cells. These single-strand breaks are primarily nicks positioned at [almost equal to]50-kbp intervals throughout the entire genome that could be efficiently labeled in situ by DNA polymerase I holoenzyme but not by Klenow fragment and terminal transferase unless after ribonucleolytic treatments. The RNA molecules involved appear to comprise R-loops, recognized by the S9.6 RNA/DNA hybrid-specific antibody. By using the breakpoint cluster region of the Mixed Lineage Leukemia (MLL) gene as a model, we have found that the number of manifest nicks detected by FISH performed after field inversion single-cell gel electrophoresis depends on epigenetic context, but the difference between germ-line and translocated MLL alleles is abolished by protease treatment. Our data imply that the double-stranded genomic DNA is composed of contiguous rather than continuous single strands and reveal an aspect of higher-order chromatin organization with ribonucleoprotein-associated persistent nicks defining [almost equal to]50-kbp domains. |
doi_str_mv | 10.1073/pnas.0702269104 |
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These single-strand breaks are primarily nicks positioned at [almost equal to]50-kbp intervals throughout the entire genome that could be efficiently labeled in situ by DNA polymerase I holoenzyme but not by Klenow fragment and terminal transferase unless after ribonucleolytic treatments. The RNA molecules involved appear to comprise R-loops, recognized by the S9.6 RNA/DNA hybrid-specific antibody. By using the breakpoint cluster region of the Mixed Lineage Leukemia (MLL) gene as a model, we have found that the number of manifest nicks detected by FISH performed after field inversion single-cell gel electrophoresis depends on epigenetic context, but the difference between germ-line and translocated MLL alleles is abolished by protease treatment. Our data imply that the double-stranded genomic DNA is composed of contiguous rather than continuous single strands and reveal an aspect of higher-order chromatin organization with ribonucleoprotein-associated persistent nicks defining [almost equal to]50-kbp domains.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.0702269104</identifier><identifier>PMID: 17848525</identifier><language>eng</language><publisher>United States: National Academy of Sciences</publisher><subject>Biological Sciences ; Cell lines ; Cell Proliferation ; Cells, Cultured ; Chromatin ; Chromatin - ultrastructure ; Chromosomes ; Comet Assay ; Comets ; Deoxyribonucleic acid ; DNA ; DNA - metabolism ; DNA Breaks, Single-Stranded ; DNA Fragmentation ; DNA polymerase ; Eukaryotes ; Fluorescence in situ hybridization ; Genomics ; Humans ; Hybridity ; In Situ Hybridization, Fluorescence ; Jurkat Cells ; Myeloid-Lymphoid Leukemia Protein - genetics ; Myeloid-Lymphoid Leukemia Protein - metabolism ; Proteins ; Ribonucleic acid ; Ribonucleoproteins - chemistry ; Ribonucleoproteins - metabolism ; RNA ; RNA - metabolism ; Saccharomyces cerevisiae - genetics ; Saccharomyces cerevisiae - metabolism ; T lymphocytes ; Yeasts</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 2007-09, Vol.104 (38), p.14964-14969</ispartof><rights>Copyright 2007 The National Academy of Sciences of the United States of America</rights><rights>Copyright National Academy of Sciences Sep 18, 2007</rights><rights>2007 by The National Academy of Sciences of the USA 2007</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c620t-5f4247e89e23bef06758464bf944f3b341e75c330e4dfa429a71ae7808c0aecc3</citedby><cites>FETCH-LOGICAL-c620t-5f4247e89e23bef06758464bf944f3b341e75c330e4dfa429a71ae7808c0aecc3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.pnas.org/content/104/38.cover.gif</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/25449067$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/25449067$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,727,780,784,803,885,27924,27925,53791,53793,58017,58250</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17848525$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Székvölgyi, Lóránt</creatorcontrib><creatorcontrib>Rákosy, Zsuzsa</creatorcontrib><creatorcontrib>Bálint, Bálint L</creatorcontrib><creatorcontrib>Kókai, Endre</creatorcontrib><creatorcontrib>Imre, László</creatorcontrib><creatorcontrib>Vereb, György</creatorcontrib><creatorcontrib>Bacsó, Zsolt</creatorcontrib><creatorcontrib>Goda, Katalin</creatorcontrib><creatorcontrib>Varga, Sándor</creatorcontrib><creatorcontrib>Balázs, Margit</creatorcontrib><creatorcontrib>Dombrádi, Viktor</creatorcontrib><creatorcontrib>Nagy, László</creatorcontrib><creatorcontrib>Szabó, Gábor</creatorcontrib><title>Ribonucleoprotein-masked nicks at 50-kbp intervals in the eukaryotic genomic DNA</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>By using a microscopic approach, field inversion single-cell gel electrophoresis, we show that preformed single-strand discontinuities are present in the chromatin of resting and proliferating mammalian and yeast cells. These single-strand breaks are primarily nicks positioned at [almost equal to]50-kbp intervals throughout the entire genome that could be efficiently labeled in situ by DNA polymerase I holoenzyme but not by Klenow fragment and terminal transferase unless after ribonucleolytic treatments. The RNA molecules involved appear to comprise R-loops, recognized by the S9.6 RNA/DNA hybrid-specific antibody. By using the breakpoint cluster region of the Mixed Lineage Leukemia (MLL) gene as a model, we have found that the number of manifest nicks detected by FISH performed after field inversion single-cell gel electrophoresis depends on epigenetic context, but the difference between germ-line and translocated MLL alleles is abolished by protease treatment. 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These single-strand breaks are primarily nicks positioned at [almost equal to]50-kbp intervals throughout the entire genome that could be efficiently labeled in situ by DNA polymerase I holoenzyme but not by Klenow fragment and terminal transferase unless after ribonucleolytic treatments. The RNA molecules involved appear to comprise R-loops, recognized by the S9.6 RNA/DNA hybrid-specific antibody. By using the breakpoint cluster region of the Mixed Lineage Leukemia (MLL) gene as a model, we have found that the number of manifest nicks detected by FISH performed after field inversion single-cell gel electrophoresis depends on epigenetic context, but the difference between germ-line and translocated MLL alleles is abolished by protease treatment. 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subjects | Biological Sciences Cell lines Cell Proliferation Cells, Cultured Chromatin Chromatin - ultrastructure Chromosomes Comet Assay Comets Deoxyribonucleic acid DNA DNA - metabolism DNA Breaks, Single-Stranded DNA Fragmentation DNA polymerase Eukaryotes Fluorescence in situ hybridization Genomics Humans Hybridity In Situ Hybridization, Fluorescence Jurkat Cells Myeloid-Lymphoid Leukemia Protein - genetics Myeloid-Lymphoid Leukemia Protein - metabolism Proteins Ribonucleic acid Ribonucleoproteins - chemistry Ribonucleoproteins - metabolism RNA RNA - metabolism Saccharomyces cerevisiae - genetics Saccharomyces cerevisiae - metabolism T lymphocytes Yeasts |
title | Ribonucleoprotein-masked nicks at 50-kbp intervals in the eukaryotic genomic DNA |
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