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

doi:10.1038/ncomms12404

PARP3 is a sensor of nicked nucleosomes and monoribosylates histone H2B^Glu2

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 language	English
Article number	12404
Journal	Nature Communications
Volume	7
Early online date	17 Aug 2016
DOIs	https://doi.org/10.1038/ncomms12404
Publication status	Published - Aug 2016

Keywords

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

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10.1038/ncomms12404

PARP3 is a sensor of nicked nucleosomesFinal published version, 3.09 MBLicence: CC BY

Cite this

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title = "PARP3 is a sensor of nicked nucleosomes and monoribosylates histone H2BGlu2",

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.",

keywords = "RCUK, MRC, MR/J006750/1, DNA repair enzymes, DNA-binding proteins, NMR spectroscopy",

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

year = "2016",

month = aug,

doi = "10.1038/ncomms12404",

language = "English",

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journal = "Nature Communications",

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T1 - PARP3 is a sensor of nicked nucleosomes and monoribosylates histone H2BGlu2

AU - Grundy, Gabrielle J.

AU - Polo, Luis M.

AU - Zeng, Zhihong

AU - Rulten, Stuart L.

AU - Hoch, Nicolas C.

AU - Paomephan, Pathompong

AU - Xu, Yingqi

AU - Sweet, Steve M.

AU - Thorne, Alan W.

AU - Oliver, Antony W.

AU - Matthews, Steve J.

AU - Pearl, Laurence H.

AU - Caldecott, Keith W.

PY - 2016/8

Y1 - 2016/8

N2 - 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.

AB - 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.

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KW - MRC

KW - MR/J006750/1

KW - DNA repair enzymes

KW - DNA-binding proteins

KW - NMR spectroscopy

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DO - 10.1038/ncomms12404

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