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10.1038/ncomms15760

http://scihub22266oqcxt.onion/10.1038/ncomms15760
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C5472794!5472794!28604675
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suck abstract from ncbi


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pmid28604675      Nat+Commun 2017 ; 8 (ä): ä
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  • Identification of the elementary structural units of the DNA damage response #MMPMID28604675
  • Natale F; Rapp A; Yu W; Maiser A; Harz H; Scholl A; Grulich S; Anton T; Hörl D; Chen W; Durante M; Taucher-Scholz G; Leonhardt H; Cardoso MC
  • Nat Commun 2017[]; 8 (ä): ä PMID28604675show ga
  • Histone H2AX phosphorylation is an early signalling event triggered by DNA double-strand breaks (DSBs). To elucidate the elementary units of phospho-H2AX-labelled chromatin, we integrate super-resolution microscopy of phospho-H2AX during DNA repair in human cells with genome-wide sequencing analyses. Here we identify phospho-H2AX chromatin domains in the nanometre range with median length of ?75?kb. Correlation analysis with over 60 genomic features shows a time-dependent euchromatin-to-heterochromatin repair trend. After X-ray or CRISPR-Cas9-mediated DSBs, phospho-H2AX-labelled heterochromatin exhibits DNA decondensation while retaining heterochromatic histone marks, indicating that chromatin structural and molecular determinants are uncoupled during repair. The phospho-H2AX nano-domains arrange into higher-order clustered structures of discontinuously phosphorylated chromatin, flanked by CTCF. CTCF knockdown impairs spreading of the phosphorylation throughout the 3D-looped nano-domains. Co-staining of phospho-H2AX with phospho-Ku70 and TUNEL reveals that clusters rather than nano-foci represent single DSBs. Hence, each chromatin loop is a nano-focus, whose clusters correspond to previously known phospho-H2AX foci.
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