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

Grundy, Gabrielle J, Polo, Luis M, Zeng, Zhihong, Rulten, Stuart, Hoch, Nicolas, Pathompong, Paomephan, Xu, Yingqi, Sweet, Steve M, Thorne, Alan W, Oliver, Antony W, Matthews, Steve J, Pearl, Laurence H and Caldecott, Keith W (2016) PARP3 is a sensor of nicked nucleosomes and monoribosylates histone H2B(Glu2). Nature Communications, 7 (12404). ISSN 2041-1723

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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.

Item Type: Article
Schools and Departments: School of Life Sciences > Sussex Centre for Genome Damage and Stability
Subjects: Q Science > QD Chemistry > QD0241 Organic chemistry > QD0415 Biochemistry
Depositing User: Gee Wheatley
Date Deposited: 26 Aug 2016 15:25
Last Modified: 07 Mar 2017 04:40
URI: http://sro.sussex.ac.uk/id/eprint/63036

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