PARP3 is a sensor of nicked nucleosomes and monoribosylates histone H2BGlu2

Gabrielle J. Grundy, Luis M. Polo, Zhihong Zeng, Stuart L. Rulten, Nicolas C. Hoch, Pathompong Paomephan, Yingqi Xu, Steve M. Sweet, Alan W. Thorne, Antony W. Oliver, Steve J. Matthews, Laurence H. Pearl, Keith W. Caldecott

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Abstract

PARP3 is a member of the ADP-ribosyl transferase superfamily that we show accelerates the repair of chromosomal DNA single-strand breaks in avian DT40 cells. Two-dimensional nuclear magnetic resonance experiments reveal that PARP3 employs a conserved DNA-binding interface to detect and stably bind DNA breaks and to accumulate at sites of chromosome damage. PARP3 preferentially binds to and is activated by mononucleosomes containing nicked DNA and which target PARP3 trans-ribosylation activity to a single-histone substrate. Although nicks in naked DNA stimulate PARP3 autoribosylation, nicks in mononucleosomes promote the trans-ribosylation of histone H2B specifically at Glu2. These data identify PARP3 as a molecular sensor of nicked nucleosomes and demonstrate, for the first time, the ribosylation of chromatin at a site-specific DNA single-strand break.
Original languageEnglish
Article number12404
JournalNature Communications
Volume7
Early online date17 Aug 2016
DOIs
Publication statusPublished - Aug 2016

Keywords

  • RCUK
  • MRC
  • MR/J006750/1
  • DNA repair enzymes
  • DNA-binding proteins
  • NMR spectroscopy

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